Prodromes and coping types in bipolar patients with nonpsychotic or psychotic mania

BackgroundBipolar disorder is a recurrent and cyclical illness frequently accompanied by psychotic symptoms. Detecting prodromes and enhancing coping skills for prodromal symptoms in bipolar patients are very important for relapse prevention. Psychotic features in bipolar patients are related to poor prognosis. We aimed to investigate the differences in prodromal symptoms and coping styles in psychotic and nonpsychotic bipolar patients.MethodsEighty-three euthymic bipolar patients with or without a history of manic psychosis were interviewed about their demographic, diagnostic, and clinical information and completed a 40-item checklist for prodromal symptoms. After the interview, they completed the Coping Inventory for Prodromes of Mania.ResultsThe differences between the psychotic patients and the nonpsychotic patients were found in the prodromal durations, and a few prodromal symptoms such as afraid of going crazy (P = .03), energetic-very active (P = .01), and hearing hallucination (P = .02). The psychotic patients showed a higher score of denial or blame than the nonpsychotic ones (1.92 ± 0.73 in nonpsychosis, 2.32 ± 0.84 in psychosis; P = .03). Logistic regression revealed that the duration of prodromes (P = .02) and hearing hallucination (P = .01) were related to the presence of psychotic features.ConclusionPsychotic patients had a tendency to use denial or blame coping strategy and to experience attenuated psychotic symptoms a little more during the prodromal period. Timely psychosocial approaches for detecting signs and enhancing coping strategies would improve the outcomes.     

Prodromal symptoms in manic depressive psychosis

Summary Twenty patients suffering from manic depressive psychosis were interviewed about the prodromes to both manic and depressive episodes. These prodromal periods were compared with a recent control period during which the patient was in remission. It was possible for 85% of patients to identify a depressive prodrome and 75% a manic prodrome. Prodromal periods were characterised by a significant increase in the number and magnitude of symptoms compared with those present during remission. The mean duration of manic prodromes was slightly longer than that of depressive prodromes (28.9 days and 18.8 days respectively). The majority of patients could identify a time sequence to the retainment of insight during their prodromes and could also identify idiosyncratic symptoms.     

Duration and symptoms of bipolar prodromes

The duration and symptoms of manic and depressive prodromes of 20 bipolar patients showed much interindividual variation. However, these features were consistent in successive episodes of the same type in the same patient. Manic prodromes were longer than depressive prodromes.     

A prospective, longitudinal study of percentage of time spent ill in patients with bipolar I or bipolar II disorders

Background:  There is a recent appreciation that patients with bipolar disorder spend a substantial period of time with minor or subsyndromal mood symptoms both manic and depressive. This study examined time spent in minor and subsyndromal mood states as well as with mania and depression in a cohort of well characterized bipolar I and II patients who were followed prospectively for an average of three years.
Method:  Detailed life-charting data were obtained from 138 patients with bipolar disorder. Mood states were characterized as euthymic, subsyndromal, minor or major affective episodes based on rigorously defined criteria. The amount of time spent in these mood states during follow-up was examined.
Results:  Patients in the total sample and within each bipolar subtype spent approximately half of their time euthymic. The remainder of the time was spent in varying severity of mood states. However, the majority of time was spent with minor and subsyndromal symptoms, both manic and depressive. Bipolar I patients differ from bipolar II in that significantly more time was spent with subsyndromal, minor and manic symptoms. There was no difference in time spent with depressive symptoms between the two groups.
Conclusions:  Patients with bipolar disorder spend a substantial proportion of time with depressive or manic symptoms with the preponderance being minor or subsyndromal. Awareness of subthreshold symptoms in bipolar disorders and treatment of such symptoms may be improved by establishing guidelines that specifically outline appropriate strategies for reducing the duration of subsyndromal symptoms in bipolar disorder.     

Psychotherapie bei bipolaren affektiven Störungen

Mood stabilisers show convincing evidence of relapse prevention in patients suffering from bipolar affective disorder. However, despite continuous medication the majority of patients suffer from relapses. It seems logical to apply principles of psychological intervention to bipolar patients. Elements of psychotherapy are: psychoeducation about symptoms, prodromal states, and course of illness; symptom monitoring; and influencing cognitive and behavioural strategies to improve symptomatology, social functioning, compliance, and relapse prevention. The goal of this review is to summarise the current status of controlled studies including psychological approaches to bipolar patients, to describe the efficacy of psychotherapy, and to address lack of knowledge and future trends in this clinical field. We located 461 reports about psychological interventions with bipolar patients but identified only 28 controlled and methodologically sound studies. In those studies 2294 patients were treated. Almost all (over 90%) fulfilled bipolar I criteria. All psychotherapies include psychoeducation and information about bipolar affective disorders and ask patients to self-monitor daily symptoms and other daily events. The majority of psychotherapies are cognitive-behaviorally oriented and treat patients in a one-to-one setting, but family oriented approaches and group settings were also prevalent. Studies show evidence that psychotherapy in combination with mood stabilizers improved depressive (to less extent manic) symptoms (d=0.39) and almost doubled the period of time between two episodes (d=0.71). Open questions are: indicators and predictors of successful outcome, length and intensity of treatment, essential elements of helpful intervention, long-term follow-up, and prevention of bipolar disorders in high-risk groups.     

Treatment of bipolar mania with risperidone

In patients with bipolar disorder antipsychotics are frequently used for the treatment of acute manic episodes, either in monotherapy, in addition to a mood stabilizer or in patients refractory to lithium or other mood stabilizers. However, a number of studies demonstrated that the use of conventional neuroleptics is restricted -- particularly for long-term treatment and relapse prevention in bipolar disorder -- due to their side effect profile and their potential to induce or worsen depressive symptoms. In contrast, atypical antipsychotics have a better tolerability profile and fewer extrapyramidal side effects. A number of clinical studies showed that the atypical antipsychotic risperidone was effective and well tolerated in the treatment of bipolar mania. This was reported both for the treatment of acute episodes and for the maintenance therapy. Recent data suggest that risperidone can be used effectively either in addition to or even instead of a mood stabilizer. This review summarizes the available literature on risperidone in the treatment of bipolar disorders.     

Lamotrigine therapy in elderly patients with epilepsy, bipolar disorder or dementia

INTRODUCTION: In spite of circumstances that precipitate high use of anticonvulsants in geriatric populations, there is a paucity of data on the use of antiepileptic drugs in elderly patients with psychiatric and neurological disorders. METHODS: Reports of lamotrigine therapy in elderly patients with epilepsy, bipolar disorder (BD), or dementia were identified by conducting an electronic search of major publication databases. Abstracts and presentations from professional meetings were searched as were the bibliographies of relevant articles. RESULTS: Fourteen reports were identified, and included well-controlled prospective trials, retrospective analyses, and case reports of lamotrigine treatment. Controlled trials in elderly patients with epilepsy demonstrate efficacy and tolerability comparable to gabapentin. Improvement in bipolar depressive symptoms, improvement in core manic symptoms, and delay in mood relapse was reported in geriatric patients with BD. Preliminary case studies in patients with dementia note improvement in cognition and symptoms of agitation and depression. CONCLUSION: Review of the available literature suggests lamotrigine is effective and well tolerated in elderly patients with epilepsy and relatively well-tolerated and may be effective in delaying mood relapse, particularly in the depressive pole, in patients with BD. While very limited literature suggests that lamotrigine may be effective and relatively well-tolerated in patients with dementia, further studies are needed.     

Changes in insight among patients with bipolar I disorder: a 2-year prospective study

OBJECTIVES: The aim of this 2-year prospective study was to examine changes in insight among bipolar patients with different clinical courses. METHODS: A cohort of 65 patients with bipolar I disorder in remission was recruited for this study. They received six follow-up assessments over a 2-year period. The Schedule of Assessment of Insight-Expanded version (SAI-E) was used to determine their levels of insight, while the Young Mania Rating Scale (YMRS) and the Hamilton Rating Scale for Depression (HAM-D) were used to determine affective symptoms. Types of changes in insight among bipolar patients were analyzed according to the different clinical courses during the 2-year follow-up period. RESULTS: Insight in consistently stable patients was steady during the 2-year period. Insight decreased during the manic period in patients with only a single manic episode as well as in those with repeated manic episodes. However, insight returned to the pre-episode level for patients with only a single manic episode, but did not for most of the patients with repeated episodes. No changes in insight were observed during depressive episodes for either patients with a single or those with repeated depressive episodes. CONCLUSIONS: The types of insight changes among bipolar patients during the 2-year period were various and depended on the different clinical courses. Frequent mood disturbance episodes may cause patient insight to deteriorate.     

What is a "mood stabilizer"? An evidence-based response

OBJECTIVE: The term "mood stabilizer" is widely used in the context of treating bipolar disorder, but the U.S. Food and Drug Administration (FDA) does not officially recognize the term, and no consensus definition is accepted among investigators. The authors propose a "two-by-two" definition by which an agent is considered a mood stabilizer if it has efficacy in treating acute manic and depressive symptoms and in prophylaxis of manic and depressive symptoms in bipolar disorder. They review the literature on the efficacy of agents in any of these four roles to determine which if any agents meet this definition of mood stabilizer. METHOD: The authors conducted a comprehensive review of English-language literature describing peer-reviewed, U.S. Agency for Healthcare Research and Quality class A controlled trials in order to identify agents with efficacy in any of the four roles included in their definition of a mood stabilizer. The trials were classified as positive or negative on the basis of primary outcome variables. An "FDA-like" criterion of at least two positive placebo-controlled trials was required to consider an agent efficacious. The authors also conducted a sensitivity analysis by raising and relaxing the criteria for including trials in the review. RESULTS: The authors identified 551 candidate articles, yielding 111 class A trials, including 81 monotherapy trials with 95 independent analyses published through June 2002. Lithium, valproate, and olanzapine had unequivocal evidence for efficacy in acute manic episodes, lithium in acute depressive episodes and in prophylaxis of mania and depression, and lamotrigine in prophylaxis (relapse polarity unspecified). Thus, only lithium fulfilled the a priori definition of a mood stabilizer. Relaxing the quality criterion did not change this finding, while raising the threshold resulted in no agents fulfilling the definition. CONCLUSIONS: When all four treatment roles are considered, the evidence supported a role for lithium as first-line agent for treatment of bipolar disorder. The analysis also highlights unmet needs and promising agents and provides a yardstick for evaluating new treatment strategies.     

Impact of antidepressant discontinuation after acute bipolar depression remission on rates of depressive relapse at 1-year follow-up

OBJECTIVE: While guidelines for treating patients with bipolar depression recommend discontinuing antidepressants within 6 months after remission, few studies have assessed the implications of this strategy on the risk for depressive relapse. This study examined the effect of antidepressant discontinuation or continuation on depressive relapse risk among bipolar subjects successfully treated for an acute depressive episode. METHOD: Eighty-four subjects with bipolar disorder who achieved remission from a depressive episode with the addition of an antidepressant to an ongoing mood stabilizer regimen were followed prospectively for 1 year. The risk of depressive relapse among 43 subjects who stopped antidepressant treatment within 6 months after remission ("discontinuation group") was compared with the risk among 41 subjects who continued taking antidepressants beyond 6 months ("continuation group"). RESULTS: A Cox proportional hazards regression analysis indicated that shorter antidepressant exposure time following successful treatment was associated with a significantly shorter time to depressive relapse. Furthermore, patients who discontinued antidepressant treatment within the first 6 months after remission experienced a significantly shorter period of euthymia before depressive relapse over the length of 1-year follow-up. One year after successful antidepressant response, 70% of the antidepressant discontinuation group experienced a depressive relapse compared with 36% of the continuation group. By the 1-year follow-up evaluation, 15 (18%) of the 84 subjects had experienced a manic relapse; only six of these subjects were taking an antidepressant at the time of manic relapse. CONCLUSIONS: The risk of depressive relapse in patients with bipolar illness was significantly associated with discontinuing antidepressants soon after remission. The risk of manic relapse was not significantly associated with continuing use of antidepressant medication and, overall, was substantially less than the risk of depressive relapse. Maintenance of antidepressant treatment in combination with a mood stabilizer may be warranted in some patients with bipolar disorder.     

Mood patterns and classification in bipolar disorder

PURPOSE OF REVIEW: The aim of this review is to highlight recent studies that have questioned the current split of mood disorders into the categories of bipolar and depressive disorders. RECENT FINDINGS: A continuity between bipolar disorders (mainly bipolar II disorder) and major depressive disorder was supported by several lines of evidence: depressive mixed states (mixed depression) and dysphoric (mixed) hypomania (opposite polarity symptoms in the same episode do not support the splitting between mania/hypomania and depression); family history, major depressive disorder is the most common mood disorder in relatives of bipolar probands; lack of points of rarity between the depressive syndromes of bipolar II disorder and major depressive disorder; bipolar features in major depressive disorder; major depressive disorder shifting to bipolar disorders; history of manic/hypomanic symptoms in major depressive disorder and correlation between lifetime manic/hypomanic symptoms and depressive symptoms in major depressive disorder; factors of hypomania inside major depressive disorder; recurrent course of major depressive disorder; depression more common than mania and hypomania in bipolar disorders; trait mood lability in major depressive disorder. SUMMARY: This review of the recent findings on the relationship between bipolar disorders (especially bipolar II disorder) and depressive disorders seems to support a continuity among mood disorders, and runs against the current classification of mood disorders dividing them into independent categories. Further research is needed in the area, in part because of its possible treatment impact.     

The relationship of major depressive disorder to bipolar disorder: Continuous or discontinuous?

Recent studies have questioned current diagnostic systems that split mood disorders into the independent categories of bipolar disorders and depressive disorders. The current classification of mood disorders runs against Kraepelin’s unitary view of manic-depressive insanity (illness). The main findings of recent studies supporting a continuity between bipolar disorders (mainly bipolar II disorder) and major depressive disorder are presented. The features supporting a continuity between bipolar II disorder and major depressive disorder currently are 1) depressive mixed states (mixed depression) and dysphoric (mixed) hypomania (opposite polarity symptoms in the same episode do not support a splitting of mood disorders); 2) family history (major depressive disorder is the most common mood disorder in relatives of bipolar probands); 3) lack of points of rarity between the depressive syndromes of bipolar II disorder and major depressive disorder; 4) major depressive disorder with bipolar features such as depressive mixed states, young onset age, atypical features, bipolar family history, irritability, racing thoughts, and psychomotor agitation; 5) a high proportion of major depressive disorders shifting to bipolar disorders during long-term follow-up; 6) a high proportion of major depressive disorders with history of manic and hypomanic symptoms; 7) factors of hypomania present in major depressive disorder episodes; 8) recurrent course of major depressive disorder; and 9) depressive symptoms much more common than manic and hypomanic symptoms in the course of bipolar disorders.     

The relationship of major depressive disorder to bipolar disorder: Continuous or discontinuous?

Recent studies have questioned current diagnostic systems that split mood disorders into the independent categories of bipolar disorders and depressive disorders. The current classification of mood disorders runs against Kraepelin’s unitary view of manic-depressive insanity (illness). The main findings of recent studies supporting a continuity between bipolar disorders (mainly bipolar II disorder) and major depressive disorder are presented. The features supporting a continuity between bipolar II disorder and major depressive disorder currently are 1) depressive mixed states (mixed depression) and dysphoric (mixed) hypomania (opposite polarity symptoms in the same episode do not support a splitting of mood disorders); 2) family history (major depressive disorder is the most common mood disorder in relatives of bipolar probands); 3) lack of points of rarity between the depressive syndromes of bipolar II disorder and major depressive disorder; 4) major depressive disorder with bipolar features such as depressive mixed states, young onset age, atypical features, bipolar family history, irritability, racing thoughts, and psychomotor agitation; 5) a high proportion of major depressive disorders shifting to bipolar disorders during long-term follow-up; 6) a high proportion of major depressive disorders with history of manic and hypomanic symptoms; 7) factors of hypomania present in major depressive disorder episodes; 8) recurrent course of major depressive disorder; and 9) depressive symptoms much more common than manic and hypomanic symptoms in the course of bipolar disorders.     

Burden of illness in bipolar depression

Bipolar depression is the underrecognized and unappreciated phase of bipolar disorder. Nevertheless, bipolar depression is responsible for much of the morbidity and mortality associated with the disorder. Depressive symptoms are far more prevalent than hypomanic or manic symptoms in bipolar patients, and they are associated with a heavier burden of illness, including reduced functioning, increased risk of suicidal acts, and high economic costs. Because most patients with bipolar disorder present with depression, misdiagnoses of major depressive disorder are common, even typical. Comorbid psychiatric disorders are also prevalent and may obscure the diagnosis and complicate treatment strategies. Depressed patients should be carefully assessed for manic or hypomanic symptoms to help reveal possible bipolar disorder. In addition to evaluation of psychiatric symptoms, a close examination of family history, course of illness, and treatment response will aid the clinician in making an accurate diagnosis. Treatment of acute depression in bipolar patients may require therapy combining agents such as lithium, divalproex, lamotrigine, carbamazepine, and atypical antipsychotics or using such agents in combination with an anti-depressant. Olanzapine/fluoxetine combination is the only medication currently approved for the treatment of bipolar depression. Antidepressant monotherapy should not be used, because there is evidence that such treatment increases the risk of switching into mania/hypomania and could induce treatment-refractory conditions such as mixed or rapid-cycling states. Maintenance therapy will be required by most patients, since discontinuation of mood stabilizers or antidepressants frequently leads to relapses in depressive symptoms. Prompt diagnosis and the use of specific therapeutic agents with evidence of efficacy may help reduce the disease burden associated with bipolar depression.     

Antiepileptic drugs and mood stability.

This paper will discuss different definitions of the term "mood stabilizer" and highlight in detail the antiepileptic drugs carbamazepine, valproate and lamotrigine with respect to their relative strengths in stabilizing mood in bipolar patients. These drugs are heterogeneous in their mechanisms of action and in their efficacy to stabilize patients with epilepsy and the various mood states in bipolar disorder. Lamotrigine has obtained approval in several countries for the indication of preventing bipolar depressive episodes, which raises the question of differential efficacy of other antiepileptic drugs as mood stabilizers in the prevention of either depressive or hypo-/manic episodes. A Medline Search to 2006 was conducted for controlled acute and maintenance studies of the three scientifically and clinically most established antiepileptic drugs carbamazepine, valproate and lamotrigine. The medications discussed in this review only partly fulfill definitions of a mood stabilizer, and we suggest that future research should focus on combined treatment strategies.     

Anticonvulsants in bipolar disorder.

In recent years, a number of anticonvulsants have been more rigorously investigated for their potential mood-stabilizing properties. They are heterogeneous in their mechanisms of action and in their efficacy in the various mood states in bipolar illness (Table 3). At present, evidence from well-controlled studies supports the role of DIV and CBZ in the treatment of acute mania. DIV seems to have better efficacy than lithium in mixed mania or mania associated with depressive symptoms and is recommended as a first-line pharmacologic option in acutely manic or mixed manic patients. Neither CBZ nor DIV have robust evidence supporting their efficacy in the treatment of acute bipolar depression, although DIV clearly possesses beneficial effects on depressive symptomatology and prophylaxis against depressive episodes during long-term treatment. Results from a large study indicate that LAM has significant efficacy in bipolar depression without the associated risks of cycle acceleration or manic/hypomanic switches. LAM should be considered a primary option in patients with bipolar depression and in bipolar II patients with rapid cycling. DIV is recommended as a first-line option in bipolar I patients with rapid cycling. LAM has proven efficacy in the prophylaxis of bipolar I disorder and should be considered along with lithium or DIV as treatment of choice in the long-term management of bipolar disorder. For the other anticonvulsants, including CBZ and OXC, there is still inadequate evidence of efficacy as monotherapy in the long-term management of bipolar disorder. Even less data exist for other available AEDs, and consensus is growing that someAEDs (eg, GBP) have little or no specific effect in bipolar disorder. Despite the progress made in the past decade, a wider therapeutic armamentarium is critically needed, because a large proportion of bipolar patients do not respond to acute treatments during a manic or depressive episode and have frequent relapse and recurrences during long-term treatment. As additional AEDs become available, rigorously designed and large-scale studies examining AEDs as monotherapy and AEDs in combination therapies versus placebo must be undertaken to assess efficacy and safety more adequately to provide better guidance for the clinician faced with the management of this challenging mood disorder.     

Depression with versus without manic features in rapid-cycling bipolar disorder

Depression has been identified as a hallmark feature of rapid-cycling bipolar disorder, although less attention has been paid to the presence of manic features accompanying depression in rapid cyclers. To provide greater information about the extent to which depression arises with or without salient manic features in rapid cycling, we conducted a preliminary study of rapid cycling in outpatients seeking treatment at an academic specialty center for bipolar disorder. Forty DSM-IV affectively symptomatic bipolar outpatients with past year DSM-IV rapid cycling underwent systematic evaluation of symptoms and illness characteristics. Manic and depressive symptoms, treatments, and clinical features were rated by standardized scales. Major depression was present in most rapid cyclers (85%), but salient manic features were also evident in half of all depressed rapid cyclers. A lifetime history of suicide attempts was significantly more common in rapid cyclers who presented with major depression plus salient manic features than in those who presented with pure depression or pure mania (p = .033). Antidepressants were being prescribed for approximately one third of depressed rapid cycling patients regardless of the presence of concomitant manic features, whereas mood stabilizers tended to be used less often when manic features accompanied depression. Depression in conjunction with manic symptoms, rather than pure depression alone, may be more common among rapid-cycling bipolar patients who seek treatment. Lifetime suicide risk may be greater among rapid cycling patients whose depression occurs in tandem with manic symptoms. Prescribing habits in the community that favor antidepressants over mood stabilizers may promote further mood destabilization in this population. Further studies with larger sample sizes are needed to affirm these provisional findings.     

A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states

Cerullo MA, Fleck DE, Eliassen JC, Smith MS, DelBello MP, Adler CM, Strakowski SM. A longitudinal functional connectivity analysis of the amygdala in bipolar I disorder across mood states. Bipolar Disord 2012: 14: 175–184. © 2012 The Authors. Journal compilation © 2012 John Wiley & Sons A/S. Objective: Bipolar I disorder is characterized by affective symptoms varying between depression and mania. The specific neurophysiology responsible for depression in bipolar I disorder is unknown but previous neuroimaging studies suggest impairments in corticolimbic regions that are responsible for regulating emotion. The amygdala seems to play a central role in this network and is responsible for appraisal of emotional stimuli. To further understand the role of the amygdala in the generation of mood symptoms, we used functional magnetic resonance imaging (fMRI) to examine a group of patients with bipolar I disorder longitudinally. Methods: fMRI was used to study regional brain activation in 15 bipolar I disorder patients followed for up to one year. Patients received an fMRI scan during an initial manic episode and a subsequent depressive episode. During the scans, patients performed an attentional task that incorporated emotional pictures. Fifteen healthy comparison subjects were also scanned at baseline and then at four months. Whole‐brain functional connectivity analysis was performed using the left and right amygdala as seed regions. Results: Significant changes in amygdala functional connectivity were found between the manic and depressed phases of illness. The right amygdala was significantly more positively correlated with the left inferior frontal gyrus during mania and with the right insula during depression. There were no significant differences in left amygdala correlations across mood states in the bipolar I disorder group. Conclusions: In the transition from a manic/mixed episode to a depressive episode, subjects with bipolar I disorder showed unique changes in cortical–amygdala functional connectivity. Increased connectivity between the insula and right amygdala may generate excessive positive feedback, in that both of these regions are involved in the appraisal of emotional stimuli. Increased correlation between the right amygdala and the inferior frontal gyrus in mania is consistent with previous findings of decreased prefrontal modulation of limbic regions in mania. These differences in connectivity may represent neurofunctional markers of mood state as they occurred in the same individuals across manic and depressive episodes.     

Adjunctive antidepressant use and symptomatic recovery among bipolar depressed patients with concomitant manic symptoms: findings from the STEP-BD

OBJECTIVE: Practice guidelines have advised against treating patients with antidepressants during bipolar mixed states or dysphoric manias. However, few studies have examined the outcomes of patients with co-occurring manic and depressive symptoms who are treated with antidepressants plus mood stabilizing drugs. METHOD: The authors compared outcomes in patients with bipolar disorder who received a mood stabilizing agent with versus without an antidepressant for a bipolar depressive episode accompanied by > or = 2 concurrent manic symptoms. The 335 participants were drawn from the first 2,000 enrollees in the National Institute of Mental Health (NIMH) Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD). Kaplan-Meier survival curves and Cox regression models were used to compare time to recovery. General linear models examined the relationship between antidepressant use or mania symptom load at the study entry and mania or depression symptom severity at the 3-month follow-up. RESULTS: Adjunctive antidepressant use was associated with significantly higher mania symptom severity at the 3-month follow-up. The probability of recovery at 3 months was lower among patients with higher baseline depression severity. Antidepressant use neither hastened nor prolonged time to recovery once potential confounding factors were covaried in a Cox regression model. CONCLUSIONS: In bipolar depression accompanied by manic symptoms, antidepressants do not hasten time to recovery relative to treatment with mood stabilizers alone, and treatment with antidepressants may lead to greater manic symptom severity. These findings are consistent with those from the STEP-BD randomized trial for pure bipolar depression, in which adjunctive antidepressants did not yield higher recovery rates than did mood stabilizer monotherapy.