Pichai Ittasakul and Punjaporn Waleeprakhon wrote the draft manuscript. Terence A Ketter revised the draft manuscript. Thus, all authors contributed to development of the manuscript, revised it critically for important intellectual content, and gave their approval of this version to be published. World Health Organization.
The World Health Report Geneva: World Health Organization; Ketter TA, editor. Handbook of Diagnosis and Treatment of Bipolar Disorders. Perceptions and impact of bipolar disorder: how far have we really come? Results of the national depressive and manic-depressive association survey of individuals with bipolar disorder.
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J Clin Psychiatry. Diagnosing bipolar disorder and the effect of antidepressants: a naturalistic study. Is bipolar disorder still underdiagnosed? Are antidepressants overutilized? J Affect Disord.
Features associated with the delayed initiation of mood stabilizers at illness onset in bipolar disorder. Am J Psychiatry. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Brazilian Portuguese validation of Mood Disorder Questionnaire.
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Compr Psychiatry. Psychiatry Res. Adaptation and validation of the Spanish version of the Mood Disorder Questionnaire for the detection of bipolar disorder. Bipolar Disord. Arch Psychiatr Nurs.
Validity of the mood disorder questionnaire: a general population study. Guidelines for the process of cross-cultural adaptation of self-report measures. Spine Phila Pa Kittirattanapaiboon P, Khamwongpin M. Journal of Mental Health of Thailand. Revelle W, Zinbarg RE. Coefficients alpha, beta, omega and the glb: comments on Sijtsma. Oxford: Oxford University Press; — Psychiatry Clin Neurosci. Turk Psikiyatri Derg.
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BMC Psychiatry. Screening for bipolar disorder and finding borderline personality disorder. Thus, all mood episodes included in these analyses were observed prospectively from the time they commenced. Survival time duration of mood episode was defined as the number of weeks until recovery from the episode, beginning with the first week of the episode. The survival analyses estimated the cumulative probability of recovery over the course of follow-up. The survival time ended with recovery from the mood episode or, for censored cases, the end of the follow-up period 25 years , withdrawal from the study, or death.
In estimating the rate of recovery, the analyses made use of all available data from all subjects, including the incomplete information from censored cases. These analyses also accounted for the varying lengths of follow-up for different subjects. A mixed-effects grouped-time survival model 29 estimated the magnitude of the association between various clinical predictors and the probability of recovery over time.
The predictors included mood episode type described earlier , severe onset of mood episode, number of prior mood episodes, and cumulative morbidity. Severe onset of mood episode was defined such that in week 1 of the episode, the subject met full criteria for major depression or mania along with psychosis or extreme impairment in functioning. Number of prior mood episodes included only those episodes observed during prospective follow-up, beginning with the intake mood episode and ending with the mood episode immediately prior to the episode that was analyzed.
Cumulative morbidity was defined as the total number of years spent ill with any type of mood episode during prospective follow-up, beginning at study intake and ending at the week prior to onset of the mood episode that was analyzed.
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The mixed-effects model accounted for the correlation among multiple, within-subject mood episodes. In this grouped-time survival model, the mood episode durations were categorized as follows: 1 to 2, 3 to 4, 5 to 13, 14 to 26, 27 to 39, 40 to 52, 53 to , and longer than weeks.
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It was implicitly assumed that the hazard likelihood of recovery was constant within any one categorized time interval. The mixed model also calculated an intraclass correlation coefficient, which estimated the within-subject consistency in duration of mood episodes, across multiple episodes without regard to mood episode type. Table 1 displays the sociodemographic and clinical characteristics of the sample at study intake.
The mean SD length of prospective follow-up was Attrition resulted from withdrawal of consent, an inability to locate or contact the subject, and death. A total of mood episodes were observed during follow-up. The median number of mood episodes per subject was 4 range, The mean SD number of episodes per subject was 5. Initially, we examined time to recovery without regard to mood episode type, ie, the different types of episodes were analyzed collectively.
Table 2 displays the proportion of subjects recovering from each of the first 5 successive recurrent mood episodes. There were subjects who had at least 1 recurrent mood episode. The Figure shows the corresponding survival curves for the duration of the first 5 recurrent mood episodes based on cumulative recovery probabilities Kaplan-Meier estimates.
The quartiles for duration of mood episode for each of the first 5 prospectively observed mood episodes were also examined. Another set of analyses examined time to recovery from each type of bipolar I mood episode. Table 3 shows the quartiles for the duration of the different types of mood episodes. The median duration of major depressive episodes, the most common type, was The median duration of major cycling episodes was approximately 3 to 14 times longer than that of episodes of pure depression or pure mood elevation, and the median duration of mixed major cycling episodes was approximately 4 to 20 times longer.
One-fourth of the mixed major cycling episodes lasted more than 7 years The cycling mood episodes major cycling, 94 mixed major cycling, and 28 minor cycling were composed of 4 possible component mood states: depression major or minor depression , mood elevation mania or hypomania , mixed state concurrent depression and mood elevation , and euthymia lasting less than 8 consecutive weeks. During these cycling episodes, the mean SD durations were 84 weeks median, 23 weeks for depression, 28 76 weeks median, 7 weeks for mood elevation, 8 52 weeks median, 0 weeks for mixed states ie, more than half the cycling episodes did not include a mixed state , and 11 44 weeks median, 2 weeks for euthymia.
The association between the hypothesized predictors and the probability of recovery from a mood episode was analyzed with a mixed-effects grouped-time survival model.
In addition, mood episode type was significantly associated with the probability of recovery. The mixed-effects model examined within-subject variability in time to recovery from one mood episode to the next without regard to mood episode type. The model yielded an intraclass correlation coefficient of 0. We examined the number of major depressive episodes and manic episodes that were treated with somatic therapy for at least 4 consecutive weeks or, in the case of episodes lasting less than 4 weeks, those that were treated for the entire duration of the episode.
For subjects with a study intake diagnosis of 1 unipolar major depressive disorder, 2 schizoaffective disorder, major depression, or 3 bipolar II disorder, the treatment analyses did not include mood episodes that occurred prior to the first prospectively observed episode of mania. The results describe the duration of bipolar I mood episodes and factors significantly associated with the probability of recovery from a mood episode. The mixed-effects model Table 4 provided a number of clinically relevant results.
First, the probability of recovery from a mood episode with severe onset was significantly decreased compared with the probability of recovery from a mood episode with less severe onset. This finding raises the possibility that mood episodes with severe onset may be more difficult to treat. Future treatment studies or secondary analyses of archival randomized controlled trial data should examine whether severe onset moderates recovery from mood episodes.
The mixed-effects model and other survival analyses Table 3 also demonstrated that there are clinically meaningful and statistically significant differences in the probability of recovery from different types of mood episodes. In particular, major cycling and mixed major cycling episodes were much longer than other types of mood episodes, consistent with previous studies showing that cycling episodes are associated with poorer outcomes compared with episodes of pure major depression or pure mania. The low intraclass correlation coefficient of 0.
For example, the intraclass correlation coefficient will be low if mood episode duration progressively decreases over time or if mood episodes are initially shorter, then longer, then shorter again. In addition, it will be low if mood episode duration progressively increases over time. The kindling model, which predicts among other things that mood episode duration will increase from one episode to the next, 33 is thus one of many competing explanations for the low intraclass correlation coefficient. This raises the possibility that there is a subgroup of subjects with kindling that can be identified and clinically characterized.
The Figure shows that the rate of recovery was fairly consistent across multiple episodes. Similar results were previously obtained in a case-register study that used hospitalization as a proxy for mood episodes. Subsyndromal symptoms were defined as 1 or 2 symptoms of a mild degree and no impairment of psychosocial functioning. The previous study 35 counted a week with subsyndromal symptoms as a week in which the subject was affectively ill, whereas the present study did not consistent with the procedures specified by Research Diagnostic Criteria 9.
This may have yielded a sample that was predisposed to have fewer depressive episodes during follow-up compared with the number of depressive episodes that occur in the general bipolar I population.
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During prospective follow-up lasting up to 25 years, the mean number of mood episodes per subject in our study was 5. In evaluating this number, it is worth noting certain aspects of the methods. First, the definition of recovery from a mood episode was relatively rigorous: at least 8 consecutive weeks with 2 or fewer mood symptoms of a mild degree and no impairment in psychosocial functioning.
Second, alternating syndromes of depression and mood elevation separated by less than 8 consecutive weeks with euthymia were counted as a single cycling mood episode. In other studies, these alternating syndromes are usually counted as separate mood episodes regardless of how little time, if any, elapses between the offset of one syndrome and the onset of the next consistent with the DSM-IV 10 and the International Statistical Classification of Diseases and Related Health Problems , 10th revision The third issue is subject selection.
Some studies recruit patients from bipolar disorder specialty clinics and may thus enroll subjects who are more resistant to maintenance treatment and therefore more vulnerable to recurrences. By contrast, the Collaborative Depression Study is strictly an observational study—treatment is not controlled by anyone associated with the study and subjects are free to pursue treatment anywhere or to forego treatment.
One limitation is that there may be other types of mood episodes beyond the ones described in this article, eg, atypical depression. Another limitation is the absence of subjects with bipolar II disorder, who may be quite vulnerable to mixed states.