Do antidepressants induce rapid cycling? A gender-specific association

OBJECTIVE: To investigate the influence of antidepressant use and gender in the genesis of rapid-cycling bipolar illness. METHOD: The charts of bipolar patients treated at the Massachusetts General Hospital Bipolar Clinic (Boston, Mass.) were reviewed for gender, presence or absence of rapid cycling, and antidepressant use prior to first mania. RESULTS: Data were obtained for 129 bipolar patients (55% women), 45% of whom had experienced a rapid-cycling course. Overall, there was no significant difference in the rates of rapid cycling between the subjects who were exposed to antidepressants prior to their first manic/ hypomanic episode and those who were not. Additional analysis carried out separately by gender found a significant association between rapid cycling and antidepressant use prior to first mania/hypomania for women but not for men. A logistic regression analysis with rapid cycling as dependent variable revealed a significant interaction between antidepressant use prior to first mania/hypomania and gender. CONCLUSION: We found a gender-specific relationship between antidepressant use prior to first manic/hypomanic episode and rapid-cycling bipolar illness. When antidepressants are prescribed to depressed women who have a risk of bipolar disorder, the risk of inducing rapid cycling should be considered. Differing proportions of women and men in previous studies may account for conflicting results reported in the literature for the relationship of antidepressants and rapid cycling. However, this naturalistic trial was uncontrolled, and controlled research is required to confirm our findings.     

Antidepressant-induced rapid cycling: another perspective.

BACKGROUND: Depressive symptoms are the main cause of morbidity in bipolar patients, but concern about antidepressant-induced rapid cycling has limited antidepressant use in such patients. This paper evaluates the validity and the prevalence of antidepressant-induced rapid cycling. METHODS: The literature regarding antidepressant induced rapid cycling is reviewed, focusing on two issues: 1) does antidepressant-induced rapid cycling occur only in patients who become manic or hypomanic on antidepressants; 2) can the apparent shortening of cycle length on antidepressants be attributable simply to the fact that antidepressants alleviate depression and can precipitate mania or hypomania. RESULTS: The suggestion that antidepressants can induce rapid cycling is derived primarily from patients who become manic or hypomanic on antidepressants. The fact that antidepressants alleviate depression and precipitate mania can explain most of the available data, without invoking the poorly defined concept of antidepressant-induced rapid cycling. CONCLUSIONS: Bipolar patients who are stable on mood stabilizers, who don't become manic or hypomanic on anti-depressants, can be safely treated with antidepressants without excessive concern about inducing rapid cycling.     

Gender differences in the phenomenology of bipolar disorder

OBJECTIVES: To investigate gender differences in the phenomenology of episodes in bipolar disorder as according to ICD-10. METHODS: All patients who got a diagnosis of a manic episode/bipolar disorder in a period from 1994 to 2002 at the first outpatient treatment ever or at the first discharge from psychiatric hospitalization ever in Denmark were identified in a nationwide register. RESULTS: Totally, 682 outpatients and 1037 inpatients got a diagnosis of a manic episode/bipolar disorder at the first contact ever. Significantly more women were treated as outpatients than as inpatients. Women were treated for longer periods as inpatients but not as outpatients. In both settings, the prevalence of depressive versus manic/mixed episodes was similar for men and women and the severity of manic episodes (hypomanic /manic without psychosis/manic with psychosis) and the severity of depressive episodes (mild/moderate/severe without psychosis/severe with psychosis) did not differ between genders. The prevalence of psychotic symptoms at first contact was the same for both genders. Among patients treated in outpatient settings more men than women presented with comorbid substance abuse and among patients treated during hospitalization more women than men presented with mixed episodes. CONCLUSIONS: Besides differences in the prevalence of mixed episodes and comorbid substance abuse few gender differences are found among patients presenting with a manic episode/bipolar disorder at first contact in psychiatric inpatient or outpatient hospital settings.     

Discriminating primary clinical states in bipolar disorder with a comprehensive symptom scale

Objective: We assessed the spectrum and severity of bipolar symptoms that differentiated bipolar disorder (BD) clinical states, employing the Bipolar Inventory of Symptoms Scale (BISS) which provides a broader item range of traditional depression and mania rating scales. We addressed symptoms differentiating mixed states from depression or mania/hypomania. Method: One hundred and sixteen subjects who met DSM‐IV‐TR criteria for BD and were currently in a depressed, manic/hypomanic, mixed episode, or recovered state were interviewed using the BISS. Results: A subset of manic items differed between mixed episodes and mania/hypomania or depression. Most anxiety items were more severe in mixed subjects. BISS Depression and Manic subscales differentiated episodes from recovered status. The majority of depression and manic symptoms differentiated mood states in the predicted direction. Mixed episodes had overall greater mood severity than manic/hypomanic episodes or depressed episodes. Conclusion: These results indicate that a small subset of symptoms, several of which are absent in DSM‐IV‐TR criteria and traditional rating scales for bipolar studies, aid in distinguishing mixed episodes from depressive or manic/hypomanic episodes. The results also support the utility of a comprehensive BD symptom scale in distinguishing primary clinical states of BD.     

Predictors of recurrence in bipolar disorder: primary outcomes from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD)

OBJECTIVE: Little is known about clinical features associated with the risk of recurrence in patients with bipolar disorder receiving treatment according to contemporary practice guidelines. The authors looked for the features associated with risk of recurrence. METHOD: The authors examined prospective data from a cohort of patients with bipolar disorder participating in the multicenter Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study for up to 24 months. For those who were symptomatic at study entry but subsequently achieved recovery, time to recurrence of mania, hypomania, mixed state, or a depressive episode was examined with Cox regression. RESULTS: Of 1,469 participants symptomatic at study entry, 858 (58.4%) subsequently achieved recovery. During up to 2 years of follow-up, 416 (48.5%) of these individuals experienced recurrences, with more than twice as many developing depressive episodes (298, 34.7%) as those who developed manic, hypomanic, or mixed episodes (118, 13.8%). The time until 25% of the individuals experienced a depressive episode was 21.4 weeks and until 25% experienced a manic/hypomanic/mixed episode was 85.0 weeks. Residual depressive or manic symptoms at recovery and proportion of days depressed or anxious in the preceding year were significantly associated with shorter time to depressive recurrence. Residual manic symptoms at recovery and proportion of days of elevated mood in the preceding year were significantly associated with shorter time to manic, hypomanic, or mixed episode recurrence. CONCLUSIONS: Recurrence was frequent and associated with the presence of residual mood symptoms at initial recovery. Targeting residual symptoms in maintenance treatment may represent an opportunity to reduce risk of recurrence.     

Preliminary results of a fine‐grain analysis of mood swings and treatment modalities of bipolar I and II patients using the daily prospective life‐chart‐methodology

Objective: The study aimed to increase the knowledge about the detailed course differences between different forms of bipolar disorder. Method: Using the prospective life‐chart‐clinician version, we compared the fine‐grain analysis of mood swings and treatment modalities of 18 bipolar II with 31 bipolar I patients. Results: During an observational period of a mean of 26 months we observed an increase of euthymic days, and a decrease of (sub)depressive and (hypo)manic days. Days in a (sub)depressed state were more frequent than days of (hypo)mania as well as days of subdepression or hypomania in comparison to days of full‐blown depression or mania. Bipolar II patients showed an increase in hypomanic days receiving more frequently antidepressants. Bipolar I patients, with a decrease of manic days, were significantly taking more often mood stabilizers. Conclusion: Treatment in a specialized bipolar clinic improves the overall outcome, but bipolar II disorder seems to be still treated sub‐optimally with a possible iatrogenic increase of hypomanic days.     

Mania compared with unipolar depression in old age.

OBJECTIVE: The goal of this study was to clarify the meaning and importance of mania in old age. METHOD: The authors conducted a retrospective study of 50 elderly patients consecutively admitted to a private mental hospital with an index episode of mania. As a comparison group, they used 50 age- and sex-matched patients with unipolar depression. They reviewed the charts of the 100 patients for family history, clinical course, and neurological disorders. Outcome was determined by contacting patients, families, physicians, institutional settings, and vital statistics records. Survival analysis compared mortality rates. RESULTS: The manic patients had a greater familial predisposition to affective disorder and were younger at first psychiatric hospitalization. For the 20 manic patients whose first affective episode was depression, an average of 15 years elapsed before mania became manifest. Eighteen of the manic patients, compared with only four of the depressed patients, had neurological disorders. The manic patients had a significantly higher mortality rate than the depressed patients; by the end of the follow-up, 25 of the manic patients, compared with 10 of the depressed patients, had died. CONCLUSIONS: Mania appears to have a poorer prognosis and to be a more severe form of affective illness than unipolar depression. The 18 manic patients with neurological disorders seemed to have "secondary mania." Subtle cerebral changes due to aging may have been responsible for the conversion to mania in the 20 patients who experienced a long latency from first depression to onset of mania. The low frequency of early-onset mania in this study group highlights the need to differentiate early- from late-onset mania.     

Antidepressant-associated mania in late life

BACKGROUND: Elderly patients can present with mania for the first time late in life, and some elders treated with antidepressants can present with mania. Clinical characteristics of antidepressant-associated mania (AAM) in late life have not been examined. OBJECTIVES: The aims of the study were to identify elders with AAM and to compare selected clinical characteristics to those of manic elders who had not been treated with an antidepressant. We hypothesized that AAM patients would have later age at presentation of bipolar disorder. METHODS: We retrospectively reviewed inpatients with manic disorder who were aged >or=60 years. The sample was selected from admissions prior to 1990. RESULTS: AAM patients (n = 11) were more often experiencing first manic episode, and they had later age at onset of first manic episode, compared to non-AAM patients (n = 46). Most of the AAM patients had been treated with tricyclic agents. CONCLUSIONS: These preliminary findings invite further investigation. Related studies may contribute to risk-benefit analyses for the use of particular antidepressants in the elderly. Also, first episode mania in late life may prove to be a useful model of vulnerability to AAM.     

A re-evaluation of the role of antidepressants in the treatment of bipolar depression: data from the Stanley Foundation Bipolar Network

Objectives: The risk‐to‐benefit ratio of the use of unimodal antidepressants (ADs) as adjuncts to mood stabilizers continues to be an area of controversy and disagreement among experts in the field. This paper reviews new data on: (1) depression in bipolar illness, (2) switch rates on ADs and (3) risks of AD discontinuation that are pertinent to the ongoing discussion and recommendations. Methods: In the first study reviewed, 258 outpatients with bipolar illness were assessed prospectively on a daily basis using the National Institute of Mental Health‐Life Chart Method^TM (NIMH‐LCM) for 1 year. In the second study, 127 bipolar depressed patients were randomized to 10 weeks of sertraline, bupropion, or venlafaxine, as adjuncts to mood stabilizers; non‐responders were re‐randomized and responders were offered a year of continuation treatment. In the final study, Altshuler et al. retrospectively and prospectively assessed the risk of depressive relapses in patients who remained on ADs after 2 months of euthymia compared with those who discontinued ADs. Results: Despite intensive naturalistic treatment, the 258 outpatients with bipolar illness followed prospectively for 1 year showed three times as many days depressed as days manic, re‐emphasizing the considerable depressive morbidity that remains in bipolar disorder despite the number of treatment options available. In the study of bipolar depressed patients randomized to one of three ADs, a range of severities and durations of hypomanic to manic switches were discerned following 175 trials of AD augmentation of treatment with a mood stabilizer. Of the acute 10‐week trials, 9.1% were associated with switches into hypomania or mania and another 9.1% with a week or more of hypomania alone (with no to minimal dysfunction). In 73 continuation phase AD trials, 16.4 and 19.2% were similarly associated with hypomanic to manic and hypomanic switches, respectively. In the Altshuler et al. studies, those who remained well on any AD for more than 2 months (only 15–20% of those initially treated) and who continued on ADs showed a lesser rate of relapse into depression over 1 year (35 and 36% in the first and second study, respectively) compared with those who discontinued their ADs (68 and 70% relapsing into depression). Surprisingly, this continuation of ADs was associated with no increase in the rate of switching into mania compared with those stopping ADs. Conclusions: These data reveal that depression and depressive cycling remain a substantial problem in some two‐thirds of intensively treated bipolar outpatients. Acute AD augmentation was associated with a modest response rate and 18.2% switched into a hypomanic to manic episode, and 35.6% of the continuation trials showed these two types of switches. Two separate studies suggest that in the very small subgroup who remain well on ADs for at least 2 months, one should consider continuation of this AD augmentation treatment, because AD discontinuation appears associated with a substantially increased risk of depression relapse over the subsequent year with no reduced risk of switching into mania.     

Self-reported quality of life across mood states in bipolar disorder

In distinction to the classic conceptualization of mania and hypomania, a growing body of work indicates that these episodes are not typically characterized by euphoric mood and sense of increased well-being, but rather by significant dysphoric symptoms. However, few data exist concerning self-perceived quality of life in mania or hypomania. Such data are important both for better understanding of the illness, and are particularly important for developing appropriate cost-utility studies. Accordingly, we hypothesized that two measures of self-reported quality of life, the mental subscale of the Short Form-12 (SF-12) and the EuroQol, would show reduced quality of life in patients in manic/hypomanic or mixed episodes, compared to those who were euthymic. Eighty-six patients with bipolar disorder from four Department of Veterans Affairs (VA) medical centers were assessed in a cross-sectional design. Mood state was categorized by physician diagnosis and separately by patient self-report using the Internal State Scale (ISS). Self-reported quality of life was quantified using the SF-12 and EuroQol. Findings were identical regardless of how mood state was determined. The SF-12 mental subscale and EuroQol differed significantly across mood states. Patients with mania/hypomania were either less than (SF-12 mental subscale) or equal to (EuroQol) euthymic patients, while patients in a mixed episode resembled those in a depressive episode on both indices. In contrast, SF-12 physical subscale scores showed no intergroup differences. These quality-of-life data provide further support for the conceptualization that mania and hypomania are syndromes characterized by reduced, rather than increased, sense of well-being and quality of life. Moreover, depressive symptoms appear to be the primary determinant of quality of life in bipolar disorder, although other factors may be associated with both depression and reduced quality of life in bipolar disorder.     

Sub‐threshold manic symptoms in recurrent major depressive disorder are a marker for poor outcome

Objective: A small but significant proportion of patients with major depressive disorder (MDD) report mild manic symptoms which are below the diagnostic threshold for a hypomanic episode. Method: We tested for an association between sub‐threshold manic symptoms and clinical outcome in almost 600 patients with recurrent MDD who also had no known family history of bipolar disorder. Results: 9.6% of this large sample had a life‐time history of sub‐threshold manic symptoms. These patients were significantly more likely to have a history of poor response to antidepressants (OR 2.84; 95% CI 1.23–6.56; P < 0.02) and more likely to have experienced psychosis (OR 2.07; 95% CI 1.05–4.09; P < 0.04). They had also experienced more depressive episodes on average (P = 0.006) and were more likely to have been admitted to hospital (P < 0.03). Conclusion: Sub‐threshold manic symptoms in patients with recurrent MDD may be a useful clinical marker for poor response to antidepressants and a more morbid long‐term clinical course.     

The efficacy of lamotrigine in rapid cycling and non-rapid cycling patients with bipolar disorder.

BACKGROUND: Patients with bipolar disorder (BD) who have rapid cycling features are often treatment refractory. Clear and conclusive evidence regarding effective treatments for this group is not available. METHODS: Patients with diagnoses of refractory bipolar disorder who were currently experiencing manic, mixed, depressive, or hypomanic episodes were treated with lamotrigine as add-on therapy (60 patients) or monotherapy (15 patients). We compared the efficacy of lamotrigine in the 41 rapid cycling and 34 non-rapid cycling patients with BD. RESULTS: Improvement from baseline to last visit was significant among both rapid cycling and non-rapid cycling patients for both depressive and manic symptomatology. For patients entering the study in a depressive episode, improvement in depressive symptomatology was equivalent in the two groups. Among patients entering the study in a manic, mixed, or hypomanic episode, those with rapid cycling improved less in manic symptomatology than did non-rapid cycling patients. Among rapid cycling patients with initial mild-to-moderate manic symptom severity, improvement was comparable to that in non-rapid cycling subjects; however, the subset of rapid cycling patients with severe initial manic symptomatology had little improvement in mania. Rapid cycling patients had earlier onset and more lifetime episodes of mania, depression, and mixed mania. CONCLUSIONS: Lamotrigine was generally effective and well tolerated in this group of previously non-responsive, rapid cycling bipolar patients.     

Strategies to reduce misdiagnosis of bipolar depression

Research over the past decade indicates that the prevalence of bipolar disorder is similar to that of major depression. The author discusses complexities in the diagnosis of bipolar disorder, especially in distinguishing bipolar from unipolar depression. Bipolar depression is associated with more mood lability, more motor retardation, and greater time spent sleeping. Early age of onset, a high frequency of depressive episodes, a greater percentage of time ill, and a relatively acute onset or offset of symptoms are suggestive of bipolar disorder rather than major depression. Because DSM-IV criteria require a manic or hypomanic episode for a diagnosis of bipolar disorder, many patients are initially diagnosed and treated as having major depression. Treatment of bipolar disorder with antidepressants alone is not efficacious and may exacerbate hypomania, mania, or cycling. It is important that clinicians be alert to any hint of bipolarity developing in the course of antidepressant therapy, especially among patients with first-episode major depression.     

Clinical features of delirious mania: a series of five cases and a brief literature review

ABSTRACT: BACKGROUND: Little is known about the cause and psychopathology of delirious mania, a type of disorder where delirium and mania occur at the same time. This condition still has no formal diagnostic classification. To provide more information about this potentially life-threatening condition, we studied five patients with delirious mania. METHODS: We describe the cases of five patients with delirious mania admitted to an acute inpatient psychiatric unit between January 2005 and January 2007, and discuss the cases in the context of a selective review of the clinical literature describing the clinical features and treatment of delirious mania. RESULTS: Two patients had two episodes of delirious mania. Delirium usually resolved faster than mania though not always the case. Delirious mania remitted within seven sessions of the electroconvulsive therapy (ECT) 002E. CONCLUSIONS: Delirious mania is a potentially life-threatening but under-recognized neuropsychiatric syndrome. Delirious mania that is ineffectively treated may induce a new-onset manic episode or worsen an ongoing manic episode, and the patient will need prolonged hospitalization. Delirious mania also has a close relationship with catatonia. Early recognition and aggressive treatment, especially with electroconvulsive therapy, can significantly reduce morbidity and mortality.     

Antidepressant-associated switches from depression to mania in severe bipolar disorder

OBJECTIVES: To determine whether switching from depression to mania is part of the natural history of bipolar illness or results from antidepressant (AD) treatment by examining bipolar patients with psychosis early in their illness course. METHODS: A multi-facility cohort of 123 first-admission inpatients, aged 15-60 years, with DSM-IV bipolar disorder (BD) with psychotic features, was followed for four years, and 76 individuals experienced at least one episode of depression. Frequency of and risk factors for switches from depression to mania, time to switch, and duration of the subsequent manic episode were examined in relation to AD use (with anti-manic and/or antipsychotic medications). RESULTS: The 76 respondents experienced 113 depressive episodes. Those prescribed ADs had more depressive episodes and spent more time depressed than non-users. A total of 23 depressive episodes in 17 respondents ended in a manic/hypomanic/mixed episode (20%). The time to switch and duration of the subsequent manic episode were not significantly different for the seven respondents and nine episodes involving AD treatment versus the 10 respondents and 14 episodes without ADs. None of the risk factors (age of onset 相似文献   

Syndromes and phenomenological subtypes underlying acute mania: a factor analytic study of 576 manic patients

OBJECTIVE: There are no factor analytic studies specifically including symptoms representative of depressive inhibition among manic patients, although Kraepelin described several mixed affective states with depressive inhibition. There is controversy as to whether atypical manic features such as aggression, psychosis, and depression are likely to coexist among manic patients. The authors' goal was to examine this controversy. METHOD: They used a standardized instrument to assess the presence or absence of 37 psychiatric symptoms in 576 consecutive inpatients who were diagnosed as having DSM-IV manic episode, nonmixed or mixed. RESULTS: A principal-component analysis followed by varimax rotation extracted seven independent interpretable factors (depressive mood, irritable aggression, insomnia, depressive inhibition, pure manic symptoms, emotional lability/agitation, and psychosis) that were relatively stable across several patient groups. A subsequent cluster analysis identified four phenomenological subtypes underlying acute mania: pure, aggressive, psychotic, and depressive (mixed) mania. Several variables, including gender, suicidality, and outcome of treatments, significantly differentiated the subtypes. CONCLUSIONS: In patients with mania, depressive inhibition may be a salient syndrome independent of depressive mood, lending some support to Kraepelin's classification of mixed manic states on the basis of the permutations of three elements-thought disorder, mood, and psychomotor activity. Depressive inhibition, together with depressive mood and emotional lability/agitation, appears to be an important phenomenological element of mixed states. Atypical manic features such as aggression, psychosis, and depression are not likely to coexist, but they are likely separately to characterize several different subtypes potentially underlying acute mania.     

Unmodified Electroconvulsive Therapy of Acute Mania: A Retrospective Naturalistic Study

In this retrospective naturalistic study, clinical records were reviewed to examine the effects of unmodified electroconvulsive therapy (ECT) in 30 manic patients at a psychiatric institute in India. Twenty of the patients were experiencing their first episode of a major mood disorder. ECT was associated with complete remission of mania in 26 (87%) of the patients. The remaining four patients were discharged home with residual hypomanic symptoms. On average, the patients received 5.4 treatments, and the duration from initiation of ECT to discharge from hospital was 12.9 days. The number of treatments was not related to age, age at onset, duration of index episode prior to treatment, or presence of psychosis. No patient developed an organic brain syndrome or sustained a bone fracture during unmodified ECT. One month follow-up data were available in 27 of the 30 patients. Recurrence of manic symptoms following discharge occurred in three (11%) patients. For those in whom 3 month follow-up data were available, all 15 were in complete clinical remission. The induced convulsion, and not repeated administration of general anesthetics, is integral to the antimanic effect of ECT.     

A 20-month, double-blind, maintenance trial of lithium versus divalproex in rapid-cycling bipolar disorder

OBJECTIVE: The authors tested the hypothesis that divalproex would be more effective than lithium in the long-term management of patients with recently stabilized rapid-cycling bipolar disorder. METHOD: A 20-month, double-blind, parallel-group comparison was carried out in recently hypomanic/manic patients who had experienced a persistent bimodal response to combined treatment with lithium and divalproex. Sixty patients were randomly assigned to lithium or divalproex monotherapy in a balanced design after stratification for illness type (bipolar I versus bipolar II disorder). RESULTS: Of the 254 patients enrolled in the open-label acute stabilization phase, 76% discontinued the study prematurely (poor adherence: 28%; nonresponse: 26% [of whom 74% remained depressed and 26% remained in a hypomanic/manic/mixed episode], intolerable side effects: 19%). Of the 60 patients (24%) randomly assigned to double-blind maintenance monotherapy, 53% relapsed (59% into depression and 41% into a hypomanic/manic/mixed episode), 22% completed the study, 10% had intolerable side effects, and 10% were poorly adherent. The rates of relapse into any mood episode for those given lithium versus divalproex were 56% and 50%, respectively; the rates were 34% and 29% for a depressive relapse and 19% and 22% for a hypomania/mania relapse. There were no significant differences in time to relapse. The proportion discontinuing prematurely because of side effects was 16% for lithium and 4% for divalproex. CONCLUSIONS: The hypothesis that divalproex is more effective than lithium in the long-term management of rapid-cycling bipolar disorder is not supported by these data. Preliminary data suggest highly recurrent refractory depression may be the hallmark of rapid-cycling bipolar disorder.     

Diagnostic subtypes of bipolar disorder in older versus younger adults

OBJECTIVE: To investigate differences in diagnostic subtypes of bipolar disorder as according to ICD-10 between patients whose first contact with psychiatric health care occurs late in life (over 50 years of age) and patients who have first contact earlier in life (50 years of age or below). METHODS: From 1994 to 2002 all patients who received a diagnosis of a manic episode or bipolar disorder at initial contact with the mental healthcare system, whether outpatient or inpatient, were identified in Denmark's nationwide register. RESULTS: A total of 852 (49.6%) patients, who were over age 50, and 867 patients, who were 50 or below, received a diagnosis of a manic episode or bipolar disorder at the first contact ever. Older inpatients presented with psychotic symptoms (35.4%) significantly less than younger inpatients (42.6%) due specifically to a lower prevalence of manic episodes with psychotic symptoms. Conversely, older inpatients more often presented with severe depressive episodes with psychotic symptoms than younger inpatients (32.0% versus 17.0%). Among outpatients, no significant differences were found between patients older than 50 years and patients 50 years of age or younger. However, a bimodal distribution of age at first outpatient contact was found with an intermode of 65 years and outpatients older than 65 years more often presented with severe depressive episodes with psychosis. CONCLUSIONS: Bipolar patients who are older at first psychiatric hospitalization (>50 years) present less with psychotic manic episodes and more with severe depressive episodes with psychosis than younger patients. The distribution of age at first outpatient contact is bimodal with an intermode of 65 years and outpatients older than 65 years more often present with severe depressive episodes with psychosis.