this study was iran 's part of a bridge ( bipolar disorders , improving diagnosis , guidance and education ) project which was a multicenter , cross - sectional diagnostic study conducted by 521 hospital - based or community psychiatrists in asia , europe and africa from april 1 , 2008 to april 30 , 2009 ( 19 ) .
as in each center , a key senior psychiatrist was selected for iran 's part as the national coordinator . to follow the policy of the main project , the participating local centers were both psychiatric departments of hospitals / hospital clinics ( roozbeh , imam hossein , razi hospitals in tehran and other university hospitals in other major cities)as well as independent psychiatric clinics running by specialist psychiatrists to provide representative impression of health care services in each area of the practice . in each psychiatric ward or clinic , 10 - 20 adult patients were included in the study .
persian translation and back translation of 32-item revised hypomania /mania symptoms checklist ( hcl-32 ) ( 20 ) and mini international neuropsychiatric interview ( mini ) ( 21 ) were performed by the authors .
three hundred and thirteen adults meeting dsm - iv - tr criteria for major depressive episode at the time of evaluation were recruited .
the participant psychiatrists completed the questionnaire provided by the committee of the main project on patients clinical features and socioeconomic variables .
the exclusion criteria were as follows : emergency situations , suicidal ideas , drug and current substance abuse , medical conditions , non - psychiatric emergencies and inability to complete the checklist ( hcl-32 ) .
socio - demographic variables as well as the following data were collected : a ) previous psychiatric history , any previous hospitalization , features of bipolar symptoms according to dsm - iv - tr criteria for bipolar disorders , any risk factors for bipolar disorders , any response to antidepressants and current treatment ; b ) family history of mania , hypomania or any bipolar features in parents , siblings or children ; c ) co - morbidity with or history of substance abuse and addictions , panic disorder , obsessive - compulsive disorder , social phobias , generalized anxiety disorders , eating disorders , borderline personality disorders and attention - deficit hyperactivity disorder using the mini questionnaire and symptoms checklist according to dsm - iv - tr . ; d)functional status determined by using the dsm defined global assessment of functioning(gaf ) ( 22 ) ; e ) completed hcl-32 ( by the patients ) .
the primary aim of this study was to determine the frequency of bipolar disorders in patients diagnosed as being in major depressive episode .
this was determined as a percentage of patients fulfilling the criteria for bipolar disorder according to the dsm - iv - tr criteria and the bipolar specifier proposed by angst et al ( 17 , 18).bipolarity specifier attributes bipolar disorder in patients who previously experienced an episode of elevated / irritable mood or increased activity which affected their social / occupational functioning or led to hospitalization , while no exclusion criteria were applied .
bipolar specifier includes all cases of bipolar 1-ii disorders and additional cases excluded by dsm - iv - tr criteria .
the following characteristics known to be associated with the diagnosis of bipolar disorders were considered as independent variables : sex , age younger than 30 at the time of development of first symptoms , seasonal pattern of mood episodes , 2 or more previous mood episodes , history of suicide attempts , presence of hypomania / mania among the first - degree relatives , manic / hypomanic switching or mood lability following antidepressant treatment , duration of current depressive episode of 1 month or less , current depressive symptoms featured atypical , mixed or psychotic and current psychiatric co - morbidities .
a multivariable stepwise logistic regression analysis was performed to assess the association of these variables with assigned bipolar diagnoses .
the strength of the association was presented as odds ratios ( ors ) with 95% confidence intervals .
all statistical tests were 2-sided and a probability level of 0.05 was established as statistically significant .
the association between an assigned diagnosis of bipolar disorder according to dsm - iv - tr or the bipolar specifier criteria and patient characteristics was explored .
socio - demographic variables as well as the following data were collected : a ) previous psychiatric history , any previous hospitalization , features of bipolar symptoms according to dsm - iv - tr criteria for bipolar disorders , any risk factors for bipolar disorders , any response to antidepressants and current treatment ; b ) family history of mania , hypomania or any bipolar features in parents , siblings or children ; c ) co - morbidity with or history of substance abuse and addictions , panic disorder , obsessive - compulsive disorder , social phobias , generalized anxiety disorders , eating disorders , borderline personality disorders and attention - deficit hyperactivity disorder using the mini questionnaire and symptoms checklist according to dsm - iv - tr . ; d)functional status determined by using the dsm defined global assessment of functioning(gaf ) ( 22 ) ; e ) completed hcl-32 ( by the patients ) .
the primary aim of this study was to determine the frequency of bipolar disorders in patients diagnosed as being in major depressive episode .
this was determined as a percentage of patients fulfilling the criteria for bipolar disorder according to the dsm - iv - tr criteria and the bipolar specifier proposed by angst et al ( 17 , 18).bipolarity specifier attributes bipolar disorder in patients who previously experienced an episode of elevated / irritable mood or increased activity which affected their social / occupational functioning or led to hospitalization , while no exclusion criteria were applied .
bipolar specifier includes all cases of bipolar 1-ii disorders and additional cases excluded by dsm - iv - tr criteria .
the following characteristics known to be associated with the diagnosis of bipolar disorders were considered as independent variables : sex , age younger than 30 at the time of development of first symptoms , seasonal pattern of mood episodes , 2 or more previous mood episodes , history of suicide attempts , presence of hypomania / mania among the first - degree relatives , manic / hypomanic switching or mood lability following antidepressant treatment , duration of current depressive episode of 1 month or less , current depressive symptoms featured atypical , mixed or psychotic and current psychiatric co - morbidities .
a multivariable stepwise logistic regression analysis was performed to assess the association of these variables with assigned bipolar diagnoses .
the strength of the association was presented as odds ratios ( ors ) with 95% confidence intervals .
all statistical tests were 2-sided and a probability level of 0.05 was established as statistically significant .
the association between an assigned diagnosis of bipolar disorder according to dsm - iv - tr or the bipolar specifier criteria and patient characteristics was explored .
from 313 patients participated in this study , 207 ( 66.1% ) were female and 106 ( 33.9% ) were male .
of the subjects , 66.1% were married , and 33.9% single , divorced or widowed .
a part of study performed in hospitals ( inpatients or outpatients ) was 37.4% and it was 62.6% in psychiatrists private clinics .
a total of 57 ( 18.2% ) patients fulfilled dsm-4-tr criteria for bipolar disorder , whereas 169 ( 53.9% ) met the bipolarity specifier criteria .
the bipolarity specifier additionally identified significant associations for manic / hypomanic states during antidepressant therapy , current mixed mood symptoms and substance use disorder .
tables 1 and 2 demonstrate variables in bipolar and unipolar subjects based on bipolarity specifier and bipolarity  other definitions  .
variables in bipolar and unipolar subjects based on hcl-32 bipolarity specifier variables in bipolar and unipolar subjects based on bipolarity  other definitions  based on dsm - iv - tr criteria , 57 patients ( 18.2% ) fulfilled the criteria for bipolar disorders . according to bipolarity specifier
all patients who met dsm - iv - tr criteria for bipolar disorders also fulfilled the criteria for the bipolarity specifier . for each bipolar symptom , rates were similar to the 2 bipolar groups .
duration of elevated and irritable mood was similar , mostly having a hypomanic episode lasting more than one week . in dsm - iv - tr criteria ,
hypomanic episodes which occurred in the presence of another disorder or during antidepressant treatment were excluded . however , in our sample , 115 patients ( 36.7% ) had experienced episodes of elevated or irritable mood triggered by antidepressants .
based on dsm - iv - tr criteria , 57 patients ( 18.2% ) fulfilled the criteria for bipolar disorders . according to bipolarity specifier ,
all patients who met dsm - iv - tr criteria for bipolar disorders also fulfilled the criteria for the bipolarity specifier .
duration of elevated and irritable mood was similar , mostly having a hypomanic episode lasting more than one week .
in dsm - iv - tr criteria , hypomanic episodes which occurred in the presence of another disorder or during antidepressant treatment were excluded . however , in our sample , 115 patients ( 36.7% ) had experienced episodes of elevated or irritable mood triggered by antidepressants .
the results of this study indicate that 18.21% of patients with major depressive episode met dsm - iv - tr criteria for either bipolar 1 or bipolar ii disorder , whereas with application of bipolarity specifier criteria , this rate increased to 53.9% .
findings suggest that bipolar features are more frequent than symptoms indicated by dsm - iv - tr .
these findings are consistent with previous studies which showed impulsivity and history of substance abuse , head trauma , or suicide attempts are increased in mania rating scale amongst depressed patients ( 23 ) . also , similar to our findings , in a recent study , two - thirds of the subjects with bipolar depressed episodes had concomitant manic symptoms , most often distractibility , flight of ideas or racing thoughts , and psychomotor agitation .
patients with any mixed features were significantly more likely to have early age at illness onset , rapid cycling in the past year , bipolar i subtype , history of suicide attempts , and more days in the preceding year with irritability or mood elevation than those with pure bipolar depressed episodes ( 24).in this study , by using bipolar specifier criteria , it was revealed that a number of variables in major depressive episode patients such as mood lability due to antidepressants , mixed mood features , borderline personality disorder , family history of bipolarity , anti depressant induced hypomanic / manic episode were associated with bipolarity . some hypomanic or even manic symptoms such as mood lability and co - morbidity with borderline personality disorder and anxiety disorders manifested more prominently during antidepressant treatment of mdd patients , are indicative of bipolarity .
nearly none of these variables are included in dsm - iv - tr criteria for diagnosing bipolar disorder which may be considered unjustified and a great pitfall for this classification . on the contrary such variables as resistance to antidepressants , atypical features , presence of psychosis , seasonality of mood episodes and postpartum onset which may be more frequent in bipolar types
inclusion of hospital and community psychiatrists in the study increases generalizability of findings that can be considered as the strength factor of the study , whereas non - random selection of clinics and psychiatrists are limitations .
although training sessions were held for all participants , another limitation might be the limited training given to psychiatrists involved in the study .
however , such training was not deemed necessary as all contributors were well - known skilled psychiatrists of different areas who were predominantly academic staff ( assistant , associate and full professors practicing and teaching in psychiatric departments of reputable universities ) , that can almost be an indicator of lack of bias . using mood stabilizers as prophylactic measures in bipolar disorders are more appropriate than those diagnosed as pure mdd patients ( 25 ) .
many patients in major depressive episode are prescribed antidepressants in routine depression management . according to our findings ,
it is confirmed that treatment using antidepressant medications in mde goes under question or at least requires detailed information to be collected .
present and past history of the patient as well as keen attention to symptoms of bipolar features should be traced attentively .
mood stabilizers can be considered more appropriate for such patients.a recent study proposed that either as mono - therapy or as adjunctive therapy to mood stabilizers , the role of antidepressants in treatment of depressive symptoms in bipolar disorders is of limited efficacy and with adverse consequences ( 26 ) .
inclusion of hospital and community psychiatrists in the study increases generalizability of findings that can be considered as the strength factor of the study , whereas non - random selection of clinics and psychiatrists are limitations .
although training sessions were held for all participants , another limitation might be the limited training given to psychiatrists involved in the study .
however , such training was not deemed necessary as all contributors were well - known skilled psychiatrists of different areas who were predominantly academic staff ( assistant , associate and full professors practicing and teaching in psychiatric departments of reputable universities ) , that can almost be an indicator of lack of bias .
using mood stabilizers as prophylactic measures in bipolar disorders are more appropriate than those diagnosed as pure mdd patients ( 25 ) .
many patients in major depressive episode are prescribed antidepressants in routine depression management . according to our findings ,
it is confirmed that treatment using antidepressant medications in mde goes under question or at least requires detailed information to be collected .
present and past history of the patient as well as keen attention to symptoms of bipolar features should be traced attentively .
mood stabilizers can be considered more appropriate for such patients.a recent study proposed that either as mono - therapy or as adjunctive therapy to mood stabilizers , the role of antidepressants in treatment of depressive symptoms in bipolar disorders is of limited efficacy and with adverse consequences ( 26 ) .
a high proportion of patients with mde also have a sub threshold hypomania or mania .
findings suggest that bipolar features are more frequent than symptoms indicated by dsm - iv - tr , and exclusion criteria of mood disorders in this classification should be revised .
dsm - iv classification appears to be too narrow or rigid to distinguish a more subtle and  softer  form of bipolar cases from pure unipolar ones .
 objectivebipolar spectrum disorders may often go undiagnosed or unrecognized . 
 the aim of this study was to determine the proportion of bipolar disorder symptoms in iranian patients with a major depressive episode.methods313 patients with a current dsm - iv - tr ( diagnostic and statistical manual of mental disorders 4th ed . 
 text rev . ) diagnosed with a major depressive episode entered this cross - sectional study . 
 thirty two items revised hypomania/ mania symptoms checklist ( hcl-32 ) was used to determine the frequency of bipolar episodes.resultsconsiderable proportion of patients ( 53.9% ) previously diagnosed as major depressive disorder fulfilled the criteria for bipolar disorder by bipolarity specifier . 
 the bipolarity specifier additionally identified significant association for manic / hypomanic states during antidepressants therapy ( p<0.0003 ) and current mixed mood symptoms ( p<0.0001)conclusionbipolar symptoms meeting the criteria for bipolar disorders in depressed patients who have not been previously diagnosed with bipolar disorder are frequent . 
 current dsm criteria may not be sufficient to diagnose more subtle or atypical forms of bipolar disorders . 
Materials and Methods
Data collection
Outcome Measures
Statistical Analysis
Results
Frequency of Bipolar Disorders
Frequency of Bipolar Spectrums
Antidepressant Therapy Patients
Discussion
Strengths and Limitations of the Study
Implications of Treatment
Conclusion