is bipolar disorder still underdiagnosed? are antidepressants overutilized

Journal of Affective Disorders 52 (1999) 135–144

Research report

Is bipolar disorder still underdiagnosed? Are antidepressantsoverutilized?

a , b c c*S. Nassir Ghaemi , Gary S. Sachs , Alice M. Chiou , Ananda K. Pandurangi , FrederickaK. Goodwin

aPsychopharmacology Research Center, Bipolar Disorder Research Program, The George Washington University, Washington, D.C.,USA

bHarvard Bipolar Research Program, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USAcInpatient Psychiatry Program, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA, USA

Received 17 February 1998; accepted 17 April 1998

Abstract

Background: Previous studies have suggested that bipolar disorder may be underdiagnosed, and that antidepressants maybe over-utilized in its treatment. Methods: Consecutively admitted patients (n 5 48) diagnosed with DSM-IV bipolardisorder, type I, (n 5 44) or schizoaffective disorder, bipolar type, (n 5 4) were interviewed systematically and their chartswere reviewed to confirm diagnosis before admission. They were then treated according to systematic structured interviewdiagnoses. These data reflect the changes in diagnoses and treatment. Results: 40% (19/48) were identified with previouslyundiagnosed bipolar disorder, all previously diagnosed with unipolar major depressive disorder. A period of 7.569.8 yearselapsed in this group before bipolar diagnosis was made. Antidepressant use was high on admission (38%) and was reducedwith acceptable treatment response rates. The adjunctive use of risperidone appeared to be a good treatment alternative.Limitations: While diagnoses were made prospectively, treatment response was assessed retrospectively, and was based onnon-randomized, naturalistic therapy. Conclusions: Systematic application of DSM-IV criteria identified previouslyundiagnosed bipolar disorder in 40% of a referred population of patients with mood disorders, all previously misdiagnosed asunipolar major depressive disorder. Antidepressants appeared overutilized and risperidone was an effective alternativeadjunctive therapy agent. 1999 Elsevier Science B.V. All rights reserved.

Keywords: Bipolar disorder; Drug therapy; Diagnosis; Nosology; Antidepressants; Treatment; Depression; Manic-depressiveillness

1. Introduction*Corresponding author. Address for correspondence: GeorgeWashington University, Department of Psychiatry, 2150 Penn-

The diagnosis and treatment of bipolar disorder issylvania Avenue, N.W., 8th Floor, Washington, D.C. 20037. Tel.:1 1-202-9942908; fax: 1 1-202-9946377. often difficult. In the recent past, it was recognized

0165-0327/99/$ – see front matter 1999 Elsevier Science B.V. All rights reserved.PI I : S0165-0327( 98 )00076-7

136 S.N. Ghaemi et al. / Journal of Affective Disorders 52 (1999) 135 –144

that patients with bipolar disorder were often con- frequently mistaken for unipolar major depressivefused diagnostically with schizophrenia (Pope and disorder? Are antidepressants utilized more frequent-Lipinski, 1978). With DSM-III and the adoption of ly than necessary and prudent? To what extent areneo-Kraepelinian nosology, this differential diag- mood-stabilizing agents used? Can the acute majornosis was more carefully defined, and by DSM-IV, a depressive episode in bipolar disorder be effectivelybroad consensus appeared to be reached in differen- treated with mood-stabilizing agents alone withouttiating bipolar disorder from schizophrenia clinically using antidepressant agents? Can the use of antide-(Goodwin and Jamison, 1990). However, since the pressants be minimized by the aggressive utilizationintroduction of newer safer antidepressant agents in of mood-stabilizing agents and other adjuncts for thethe past decade, there may have been an increase in treatment of bipolar disorder (particularly, typicalthe diagnosis and treatment of major depression, and atypical neuroleptic agents, and clonazepam)?perhaps in part related to the introduction of treat-ments for the diagnosis (‘‘treatment-oriented ob-servation bias’’ or Klerman’s ‘‘pharmacocentric viewof the world’’) (Stoll et al., 1993). While this factor 2. Methodsis only one of a variety of possible explanations forthis cohort effect, the move towards more aggressive Charts of all consecutive patients with the hospitaldiagnosis and treatment of depression may explain diagnosis of bipolar disorder, type I (n 5 50) orreports of possible overutilization of antidepressants schizoaffective disorder, bipolar type (n 5 5) hos-in the treatment of bipolar disorder (Wehr and pitalized on an affective disorders unit over 12Goodwin, 1987; Sachs, 1996). This overutilization of months in an urban academic hospital were re-antidepressants has been associated with increased viewed. Seven patients were excluded from furtherrisk of drug-induced mania (30–70% of patients with analysis due to experiencing a first manic episodebipolar disorder treated with antidepressants alone) (n 5 2) or not previously seeking psychiatric treat-(Goodwin and Jamison, 1990) and possible worsen- ment (n 5 5). The final sample thus consisted of 48ing of the long-term course of bipolar disorder by the patients, 44 with bipolar disorder, type I and fourinduction of treatment-resistant rapid-cycling epi- with schizoaffective disorder, bipolar type.sodes (26–51% of patients with bipolar disorder This consecutive sample of patients admitted totreated with antidepressants chronically) (Kukopulos the hospital was interviewed with a semi-structuredet al., 1983; Wehr and Goodwin, 1987; Altshuler et checklist of DSM-IV criteria and a diagnosis wasal., 1995; Kukopulos et al., 1980; Quitkin et al., made. The treatment that the patients received was1981). There is some evidence that patients with based on that diagnosis. This was then compared tomilder variations of bipolar disorder, such as type II, the diagnosis that was made by the referring physi-may be at more risk of misdiagnosis as unipolar cian or that the patients themselves were told theymajor depressive disorder and overtreatment with possessed when they came to the hospital. Dataantidepressants resulting in a worsened rapid-cycling included in this assessment came from three sourcescourse (Altshuler et al., 1995). where available: repeated clinical interview with the

Experts in the treatment of bipolar disorder have patient, outside report from family, case managers,thus recommended careful diagnosis and avoidance or other clinicians, and review of previous hospitalof antidepressant treatment except in the brief short- records.term treatment of severe acute bipolar depression in Treatment response was judged retrospectivelyconjunction with mood-stabilizing agents (Goodwin using the Clinical Global Impression scale of Im-and Jamison, 1990; Stoll et al., 1993; Sachs, 1996). provement (CGI-I). Other clinical and demographicWe wished to assess the standard of care in one data gathered at chart review were the following:community for the diagnosis and treatment of bipolar age, sex, race, family history of psychiatric illness,disorder, with special attention to the above recom- presence of comorbid personality disorders, currentmendations. We asked the following questions: Is substance abuse status, length of hospitalization, agebipolar disorder underdiagnosed, and if so, is it of 1st episode of illness, number of years ill,

S.N. Ghaemi et al. / Journal of Affective Disorders 52 (1999) 135 –144 137

Table 2presence of psychosis, years to diagnosis of bipolarDiagnostic and treatment characteristics of the sample (n 5 48)disorder, medications on admission, evidence of pastDiagnoses before admission % (n)noncompliance, discharge mood stabilizer levels, and

whether the patient was discharged against medical Bipolar disorder 56 (27)advice. Medication treatments before admission, on Unipolar disorder 40 (19)

Schizophrenia 2 (1)admission, and at discharge were also assessed.Schizoaffective disorder 2 (1)Statistical analyses consisted of unpaired and

paired t-tests, and Fisher’s exact tests. Discharge diagnoses: Bipolar subtype or schizoaffectiveDepressed 21 (10)Manic 29 (14)Mixed 21 (10)3. ResultsRapid-cycling 21 (10)Schizoaffective (manic) 8 (4)

Clinical and demographic characteristics of the Ever treated with mood stabilizers 71 (34)sample are provided in Table 1. Treated with mood stabilizers on admission 38 (18)

Table 2 describes the diagnostic and treatment Treated with mood stabilizers on discharge 96 (46)Ever treated with antidepressants 75 (36)characteristics of the sample. Most patients were notTreated with antidepressants on admission 33 (16)previously diagnosed with bipolar or schizoaffectiveTreated with antidepressants on discharge 8 (4)

disorder. The most common previous diagnosis was Ever treated with neuroleptics 52 (25)unipolar major depressive disorder. The majority of Treated with neuroleptics on admission 23 (11)patients were not receiving treatment with mood- Treated with neuroleptics on discharge 50 (24)

stabilizing agents, 1 /3 were receiving treatment withantidepressant agents, often without mood-stabilizingagents. 71% had received mood-stabilizing agents, therapeutic (lithium 0.7160.17, valproateand slightly more had received antidepressant medi- 69.1621.8, and carbamazepine 7.562.4).cations, at some time in their treatment history. Fig. 1 illustrates the time that passed from theAlmost all patients were successfully put on mood- patients’ first mental health professional contact untilstabilizing medications and taken off antidepressant diagnosis of bipolar disorder was made. In the 57%agents by discharge, with an increase in use of (25/44) of patients with bipolar disorder who were(mainly atypical) neuroleptic agents compared to previously diagnosed before admission into theadmission. Discharge mood stabilizer levels were study, bipolar diagnosis was made within the first

Table 1Clinical and demographic characteristics of the sample (n 5 48)

Race (%) Sixty-nine Caucasian, twenty-seven African–American,four Hispanic or Asian

Gender (% female) 71Age (mean 6 SD years) 36.269.6Age at first episode (mean 6 SD years) 23.469.8Years ill (mean 6 years) 12.768.1Comorbid substance abuse (%) 48Comorbid personality disorder (%) 38History of medication noncompliance (%) 66Psychosis present (%) 27Definite family history of 19diagnosed bipolar disorder (%)Family history of any 42psychiatric illness (%)Ave. length of stay (mean 6 SD days) 9.167.5Discharged against medical advice (%) 8


Fig. 1. Years to bipolar diagnosis from first contact with a mental health professional (psychiatrist or psychotherapist) in those previouslydiagnosed with bipolar disorder (n 5 25) vs. those with other diagnoses (all unipolar major depressive disorder) before study (n 5 19).

year of mental health treatment (0.962.2 years). In entire sample of patients treated with any moodthe 43% (19/44) of patients with bipolar disorder stabilizing agent alone or in combination withwho did not get diagnosed until entry into this study another mood stabilizer (valproate plus lithium was(all of whom were previously diagnosed with unipo- the main combination used), clonazepam, typicallar major depressive disorder), 7.569.8 years elapsed neuroleptic agents, and risperidone. As shown in thebefore the diagnosis of bipolar disorder was made figure, the combination of mood-stabilizing agent(t 5 2.96, df 5 41, P 5 0.005, paired t-test). with risperidone compared favorably to the other

By discharge, 63% (n 5 30) of the sample was treatment groups, particularly the neuroleptic-treatedtreated with valproate, 27% (n 5 13) with lithium, and clonazepam-treated groups.and 19% (n 5 9) with carbamazepine, with some Among ten bipolar patients with acute majortreated in combination. Two patients refused any depressive episodes, five showed moderate improve-medication treatment on discharge against medical ment. Eight were admitted on antidepressants, butadvice. The three most common treatment choices only two were discharged on them. All receivedwere valproate plus adjunct (30%), valproate alone mood stabilizers on discharge. Lithium monotherapy(20%), and lithium and anticonvulsant6adjunct was effective in 2/2 patients, and valproate mono-(13%). The most common adjuncts were ‘‘typical therapy in 1/3 patients. When those treated withneuroleptic’’ (30%), risperidone (22%), and adjuncts are included, lithium-treated bipolar de-clonazepam (17%). Only two patients (4%) were pressed patients seemed to respond somewhat betterdischarged with antidepressant treatment. Response (4 /5) than valproate-treated patients (1 /5), althoughrates (defined as moderate to marked improvement this difference was not statistically significant (P 5

on the CGI scale (score . 2)) were the same (50%) 0.21, Fisher’s exact test).across bipolar subtypes: acute bipolar depression(n 5 10), acute pure mania (n 5 16), acute mixedepisodes (n 5 14), and rapid-cycling episodes (n 5

10). All four patients with acute mania as part of 4. Discussionschizoaffective disorder responded.

Fig. 2 summarizes treatment response in the These results support the suggestion that bipolar


Fig. 2. Treatment response to mood-stabilizing agents and adjunctive treatments (n 5 46). Two patients refused treatment. Treatmentresponse was based on the use of the specific agent (e.g., clonazepam) with any other combination of treatment i.e., (along with a moodstabilizer). Thus, there is some overlap in treatment groups in patients treated with two or more adjuncts simultaneously, and the sample

**sizes above add up to more than the 46 patients treated. Differences between risperidone 1 mood stabilizer and typical NL 1 moodstabilizer, and between risperidone 1 mood stabilizer and clonazepam 1 mood stabilizer were statistically significant (P , 0.05, Fisher’sexact test).

disorder is underdiagnosed. 40% of those patients mood-stabilizing agents, with a 50% response ratewho were diagnosed with bipolar disorder in this across the board in all bipolar subtypes, includingstudy had not been previously diagnosed with it acute bipolar depression. These results suggest that(excluding first episode patients and those who did antidepressant use can be reduced with clinicalnot seek previous treatment), and all of them were improvement even in acutely depressed bipolarpreviously diagnosed with unipolar major depressive patients, at least in short-term treatment. In addition,disorder. In those who were diagnosed with con- among adjunctive treatments used, the two mostditions other than bipolar disorder, about 7.5 years promising approaches appeared to be adjunctiveelapsed from their first mental health professional treatment with atypical antipsychotic agents likecontact until the diagnosis of bipolar disorder was risperidone and the combination of mood stabilizersmade. Further, mood stabilizing agents appeared such as valproate plus lithium.underused in these patients, with only around one- To our knowledge, this is the first clinical study ofthird of patients taking them prior to hospitalization. the relationship between the diagnosis of bipolarPart of this underuse may involve patient non-com- disorder in the community and subsequent rediag-pliance, but part of it probably also was related to nosis in an academic center specializing in thelack of appropriate diagnosis of bipolar disorder. disorder. The only other data that bears on this issueOne-third of these patients were also taking antide- is from a survey of members of the Nationalpressants on admission. By discharge, all but 8% Depressive and Manic Depressive Association, whowere off antidepressants and all but 4% were on reported that they saw 3.3 psychiatrists on average


over about 8 years before being diagnosed with that families reported prodromal behavioral symp-bipolar disorder (Anonymous, 1993). The present toms of mania twice as frequently as patients, whileclinical study, in which the diagnosis of bipolar the two sources did not differ for depressive symp-disorder was made with DSM-IV criteria applied toms. Lastly, since patients frequently seek assis-prospectively to each patient, is consistent with the tance while acutely depressed, it is possible thatNDMDA survey results; that is, we found that about previous histories of manic symptoms were not8 years elapsed between initial clinical evaluation elicited by clinicians who focused mainly on currentand the eventual bipolar diagnosis. symptomatology (Goodwin and Jamison, 1990). This

How these data relate to community diagnoses would lead to underdiagnosis particularly in bipolarcannot be judged, but they clearly indicate an depressed and mixed bipolar patients, where con-underdiagnosis of bipolar disorder in this population. firming major depressive symptoms may not haveThe explanation for this difference could be varied. been followed by careful examination of manicClinical studies suggest that 35–60% of bipolar symptoms. Again, Kraepelin’s appraoch of em-patients may experience at least one major depres- phasizing longitudinal data, along with cross-section-sive episode before their first manic episode. In this al data, possesses diagnostic value.study, patients with first manic episodes were ex- Clinicians need to know that there are clinicalcluded and most patients were ill for over a decade considerations which assist in the diagnosis of(mean duration of illness 12 years), making the first bipolar disorder. Akiskal and Puzantian (1979) havefactor an unlikely one. Also, in females, depressive identified a number of possible clinical features thatepisodes tend to predominate over manic episodes, may confuse the diagnosis: incomplete interepisodewhereas in males the reverse is often the case. recovery can be confused with the declining course(Goodwin and Jamison, 1990) There was a predomi- of schizophrenia; a rapid-cycling course impedesnance of female patients in the sample, suggesting recognition of the classic recurrent course withthat this may, in part, explain the underdiagnoses. episodic recovery; the predominance of irritabilityAnother important clinical factor leading to mis- rather than euphoria may lead to underdiagnosis ifdiagnosis is lack of insight on the part of patients euphoria is one’s diagnostic standard; mixed stateswith bipolar disorder, especially during manic epi- can be difficult to distinguish from agitated depres-sodes, which keeps them from seeking assistance sion; superimposed substance abuse (which occurs inwhen manic or from reporting past manic symptoms 60% of patients at some point in life; Brady andwhen they do visit a clinician. It has been shown that Sonne, 1995) can confuse the presence of manicabout one-half of patients in an acute manic episode symptoms; flight of ideas may be mistaken forhave moderate to severe impairment of insight formal thought disorder; and excessive reliance on(Ghaemi et al., 1995). In addition, perhaps clinicians Schneiderian criteria will lead to overdiagnosis ofdo not ask about current or past manic symptoms in schizophrenia. We would also add that rapid-cyclinga systematic manner. The seven criteria described in bipolar disorder may be confused with chronicDSM-IV may not be applied as frequently as the 8 unipolar depression or borderline personality disor-major depressive criteria (Sprock, 1988), simply due der (Bolton and Gunderson, 1996). If clinicians areto a lack of education regarding them. In this study, aware of these phenomenological varieties of bipolarwe simply applied those criteria to each patient, and disorder, a certain amount of misdiagnosis might bewe noted a marked increase in diagnosis of bipolar avoided.disorder. Also, we relied on outside information A simple consideration that needs to be mentioned(chart, family report, with patient consent) in addi- is applying the manic criteria in themselves withtion to the patient interview; such information may each patient that is being screened for mood dis-not be obtained frequently, perhaps due to excessive orders. The DIGFAST mnemonic (Table 3) has beenconfidentiality concerns. In the Iowa 500 study helpful to generations of residents at McLean Hospi-(Tsuang et al., 1980), it was found that including tal. Even if applied assiduously, the criteria forinformation outside of the clinical interview in- bipolar disorder as stated in DSM-IV have beencreased diagnostic rates of bipolar disorder three- criticized for being too narrow. Akiskal (1996), forfold. Further, one study (Keitner et al., 1996) found instance, has suggested that a spectrum of conditions


Table 3The DIGFAST mnemonic for mania

Distractibility – the inability to maintain one’s concentration, as opposed to the decreasedconcentration of depression, where one is unable to initiate concentration. In mania, thisleads to multiple tasks, none of which are finished; and in depression, no task can bestarted easily.

Insomnia – decreased need for sleep, as opposed to the decreased sleep of depressive insomnia.the patients sleeps less, but has intact or increased energy the next day.

Grandiosity – can be inflated self-esteem as well, need not be delusional

Flight of ideas – the subjective experience of racing thoughts

Activities – increased goal directed activities (social, sexual, school, work, home activities); theseare goal-directed and thus not dysfunctional. Increased libido is either not expressed inactivity or associated with increased activity with one’s usual sexual partner.

Speech – pressured; this is an objective sign observed on the mental status examination. Asubjective alternative is increased talkativeness, which is determined by asking the patientor others whether the patient has been more talkative than usual (when euthymic).

Thoughtlessness – this refers to increased pleasurable activities with potential for painfulconsequences. Four stereotypic behaviors that may be asked about are sexualindiscretions, spending sprees, impulsive traveling, and reckless driving.

The diagnosis of mania is made when euphoric mood is present for one week with three of the DIGFAST symptoms, or irritable mood ispresent for one week with four of the DIGFAST symptoms, and there is significant social or occupational dysfunction. If there is nosignificant dysfunction, and the symptoms last four days at least, the diagnosis of hypomania is made. If the symptoms last less than fourdays, or if they are only present with antidepressant medications, a diagnosis of bipolar disorder, NOS, may be made. Credit this adaptationto S.N. Ghaemi, 1998.

constitute bipolar illness, and may involve similar (less than 6 hours /night)’’ and highly energetic,pathophysiologies and treatment response charac- among other characteristics suggested by Akiskal.teristics (Table 4). Specifically, assessing patients’ Patients with cyclothymic temperament have theinterepisodic personalities may be relevant. Hyper- same hypomanic baseline personality, alternatingthymic temperament is characterized by a permanent with mildly depressive symptoms that do not meethypomanic state at baseline personality, outside of criteria for major depressive episodes. If baselinespecific mood episodes; these patients are ‘‘cheerful personalities are thus examined, perhaps a goodand exuberant, extroverted, habitual short sleepers number of patients currently diagnosed with unipolar

Table 4aThe bipolar spectrum

Subtype Description

Bipolar I At least one manic episode

Bipolar II Recurrent major depression with hypomaniaand/or cyclothymic temperament

Bipolar III (NOS) Recurrent major depression without spontaneoushypomania but often with hyperthymic temperamentand/or bipolar family history

Unipolar major depression No evidence for hypomania, cyclothymia, hyperthymicpersonality, or family history of bipolar disorder

aBased on Akiskal, 1996.


depression would be rediagnosed in the ‘‘soft’’ skills of the researchers, as discussed in the methodsbipolar spectrum. While these considerations are section. Second, the data on previous treatments andrelevant to any discussion of the nosology of bipolar symptoms are limited since they are based on adisorder, it should be noted that the underdiagnosis retrospective chart review; one would expect thatdocumented in this paper involved classic type I such data would be limited by only revealing symp-bipolar patients, suggesting that broadening our toms or treatments that were relatively severe andnosology of the bipolar spectrum would reveal even thus remembered by patients or available via hospitalmore underdiagnosis than suggested in this paper. charts. Thus, the finding about the length of time thatTable 4 most clearly delineates how unipolar major elapsed from first known professional contact untildepression is essentially a diagnosis of exclusion, diagnosis of bipolar disorder may be, if anything, anonce mania, hypomania, cyclothymia, hyperthymia, underestimation of the time period involved. Third,and a bipolar family history are excluded. Our study the data regarding treatment outcome during hos-would suggest that the clinical effort required to pitalization is limited due to being retrospective,make these exclusions is sometimes not successfully uncontrolled, and limited to acute treatment withoutachieved. follow-up data after discharge; thus, one would have

These findings regarding difficulties in the diag- to view these data as limited and representative onlynosis of bipolar disorder are consistent with the of the acute inpatient naturalistic setting, needing toobserved treatment findings. As in a number of be confirmed with prospective, controlled methods.previous studies, antidepressant agents appeared They serve nonetheless to make the point that bipolaroverused in the treatment of bipolar disorder. In disorder can be treated in this setting in the manneragreement with some other reports (Goodwin and suggested. Fourth, the absence of some statisticallyJamison, 1990; Davis et al., 1996), mood stabilizing significant treatment differences among adjunctivetreatment appeared to exert moderate antidepressant treatments may be due to the limitations just noted ofeffects that were clinically helpful. Also, as in a the uncontrolled naturalistic setting, but also it maynumber of previous studies, the use of atypical be influenced by the small sample sizes and resultingantipsychotic agents like risperidone (Tohen et al., increased probability of type II error.1994; Jacobsen, 1995; Ghaemi et al., 1997) and thecombination of mood stabilizing agents (valproate

5. Conclusionsplus lithium in particular) (Solomon et al., 1997)appeared clinically effective in this naturalistic set-

These results support the conclusion that bipolarting. This would suggest that a good treatment

disorder is underdiagnosed and frequently misdiag-paradigm for bipolar disorder would be to aggres-

nosed as unipolar major depressive disorder. If notsively maximize mood stabilizing agents, combining

diagnosed early, patients with bipolar disorder re-them where necessary, and adding atypical antipsy-

main undiagnosed for 7.5 years. Patients with bipolarchotic agents like risperidone as adjunctive agents.

disorder are not adequately treated with mood stabi-Antidepressant agents might be reserved for those

lizers in the community, and appear over-treatedwho do not show an antidepressant response to

with antidepressant medications. Aggressive use ofaggressive combination treatments after one to three

mood stabilizing agents produced acute responsemonths of pure chronic depression, and then tapered

rates that were as good for depression, mixed states,within one month of euthymia (Sachs, 1996). An

and rapid-cycling as for pure mania. The addition ofalgorithm derived from this study, the research

atypical neuroleptic agents to mood-stabilizingliterature, and our clinical experience, is included in

agents appeared to be among the more effectivethe appendix as a guide for clinical practice.

adjunctive treatments.

4.1. Limitations of the current study

AcknowledgementsThere are a number of limitations to the current

report. First, the diagnostic rates obtained are based This study was supported by a grant from Abbotton the diagnostic methods and clinical interviewing Laboratories.


Appendix

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Anonymous, 1993. National survey of NDMDA members findscurrent data available. Stage IV may be moved up tolong delay in diagnosis of manic-depressive illness. Hospitalearlier stages after stage I depending on the clinicaland Community Psychiatry 44, 800–801.setting (such as markedly suicidal hospitalized de-

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is bipolar disorder still underdiagnosed? are antidepressants overutilized

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