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Frequency of psychiatric comorbid symptoms in bipolar disorder patients in remission
Aarshie Koul, A Siddharth Shetty
Department of Psychiatry, Father Muller Medical College Hospital, Mangalore, Karnataka, India
|Date of Submission||24-Dec-2020|
|Date of Decision||16-Mar-2021|
|Date of Acceptance||05-Jul-2021|
|Date of Web Publication||21-Dec-2021|
Department of Psychiatry, Father Muller Medical College Hospital, Mangalore, Karnataka
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Psychiatric comorbidity has been detected in one-third of bipolar patients. The illness itself may be a precipitating factor for developing substance use and anxiety disorders. Comorbid anxiety disorders with bipolar disorder (BD) are associated with decreased chances of recovery, poorer role functioning, and quality of life, and greater likelihood of suicide attempts. Hence, identifying comorbid symptoms in remitting patients has important preventive and therapeutic implications. Aims: The aim of the study was to estimate the frequency of psychiatric comorbid symptoms in patients of bipolar affective disorder in remission and to identify its relationship with sociodemographic variables. Methodology: This is a cross-sectional study conducted in Father Muller Medical College and Hospital, Mangalore (April 2019–July 2019), which included 90 patients aged 18–50 years with BD, manic, or depressive episodes in remission for 8 weeks who were evaluated using mini international neuropsychiatric interview plus, Hamilton rating scale for depression, and young mania rating scale. Sociodemographic details were assessed by a semi-structured pro forma. The data were analyzed using frequency, Chi-square test, and t-test. Results: Most common psychiatry comorbid symptoms seen in BD were found to be drug dependence/abuse (n = 31), second most common being alcohol dependence/abuse (n = 21), followed by suicidality (n = 8), antisocial personality, social phobia, panic disorder, and agoraphobia. Significance was found for suicidality, agoraphobia, and social phobia if the last episode was depressive and for suicidality if index episode was depressive and if age of onset was >40 years. Conclusion: Psychiatric comorbidities in BD may worsen the course and prognosis of the disorder and hence, clinicians must maintain a high index of suspicion for them. Furthermore, comorbidities may need to be identified and appropriate interventions employed to prevent iatrogenic complications.
Keywords: Bipolar disorder, comorbidity, remission
Comorbidity, by definition, indicates the occurrence of two or more syndromes in the same patient, and diagnosis of one does not exclude the diagnosis of the other.
Bipolar disorder (BD) is characterized by repeated episodes, in which patient's mood and activity levels are significantly disturbed.
Response in BDs was defined as a 50% reduction in a score from a standard rating scale of symptomatology from an appropriate baseline, regardless of index episode type (manic, depressed, or mixed). In addition, the other polarity of symptomatology cannot be significantly worsened during response phase. Remission, on the other hand, was defined as absent or minimal symptoms of both mania and depression for a duration of at least 1 week. Sustained remission required at least eight consecutive weeks of remission, up to 12 weeks., In our study, remission was defined if there were minimal or absent affective symptoms for at least 8 weeks.
Although, the direction of causality is uncertain, an association is seen between BD and anxiety disorders, attention-deficit/hyperactivity disorder, eating disorders, cyclothymia as well as other axis II personality disorders.
Psychiatric comorbidity has been detected in 31% of bipolar patients with a higher number of mixed features, depressive episodes and suicide attempts, and a predominance of depressive onset. One of the reasons for the psychiatric comorbidity could be a common genetic basis of these disorders. The illness itself may be a precipitating factor for developing substance use and anxiety disorders. Life-time comorbid anxiety disorders are seen to occur in over one-half of the bipolar patients, and are associated with younger age at onset, decreased chances of recovery, poorer role functioning and quality of life, less time euthymic, and greater likelihood of suicide attempts. Comorbid anxiety exerts an independent, deleterious effect on functioning including history of suicide attempts.
In a field research, to investigate the prevalence rates, psychiatric comorbidity in patients with BD, findings showed a lifetime prevalence rate of BD to be 0.71% for BD-I, to be 0.43% for BD-II, and 0.14% for cyclothymic disorder. Anxiety disorders were found in 30% of patients, and personality disorder in 50%.
Munoli et al. who studied comorbidity in BD and found psychiatric comorbidities in 52 (43.3%) of the sample, the most common being substance use disorder (27.5%). Comorbid physical illness was present in 77 (64.2%) patients, cardiovascular disorders being the most frequent physical illness in the sample (20%).
In another study, cross-sectional demographic, clinical, and functional ratings for 330 veterans hospitalized for BD with mini-mental state score >or = 27 and without active alcohol/substance intoxication or withdrawal, who had had at least two prior psychiatric admissions in the past 5 years, showed current depressed/mixed episode, number of past-year depressive episodes, and current anxiety disorders, but not with medical comorbidity, number of past-year manic episodes, current substance disorder, or lifetime comorbidities.
The aim of the present study is to estimate the frequency with which psychiatric comorbid symptoms are seen in patients of bipolar affective disorder in remission. This study will also attempt to find out whether sociodemographic variables affect psychiatric comorbid symptoms in BD patients.
| Methodology|| |
It is a hospital-based cross-sectional study which was conducted in Father Muller Medical College and Hospital, Mangalore, which is a tertiary care center in 2020. Participants were selected by convenient sampling out of those attending psychiatry outpatient department as a follow-up. The sample size (N) was 90 subjects which included those who met the inclusion and exclusion criteria and consented to enroll in the study. The data were collected after clearance from the institutional ethics committee.
Patients aged between 18 and 50 years with a diagnosis of bipolar affective disorder according to international classification of diseases-10 (ICD 10), in remission for a period of at least 8 weeks were included in the study. Remission was confirmed by young mania rating scale (YMRS) score of ≤7 and Hamilton rating scale for depression (HAM-D) score of ≤7. Patients with comorbid medical illnesses before the diagnosis of bipolar affective disorder were excluded from the study.
Each participant was assessed using the following instruments – mini international neuropsychiatric interview (MINI) Plus version 5.0 to assess psychiatric comorbidities, Hamilton depression rating scale-17 item version (HDRS or HAM-D) to rule out current depressive episode in subjects, and YMRS to rule out a current manic episode. The use of HAM-D and YMRS also helped ensure the selection of only those participants who were currently in remission. Furthermore, other details were also collected which included duration elapsed since the last episode, duration of illness, number of past episodes and the polarity of index and last episode, past history of other medical comorbid conditions and family history as well as data on age, education, occupation, average monthly income, marital status, and type of family using a semi-structured pro forma.
The HDRS (also known as the HAM-D) is the most widely used clinician-administered depression assessment scale which requires 20–30 min to be rated. Its main purpose was to assess severity of, and change in, depressive symptoms. The original version contains 17 items (HDRS17) pertaining to symptoms of depression experienced over the past week. Eight items are rated on a Likert scale of 0–2, one item from 0 to 3 and remaining 8 items are rated 0–4 on Likert scale. For the HDRS17, a score of 0–7 is generally accepted to be within normal, i.e., in clinical remission, while a score of 20 or higher indicates at least moderate severity.,,
YMRS, on the other hand, is one of the most frequently utilized rating scales to assess manic symptoms. It is an eleven-item clinician-rated scale which is used to measure the presence and severity of mania and associated symptoms based on the patient's subjective report of his or her clinical condition over the previous 48 h. There are four items that are graded on a 0–8 scale (irritability, speech, thought content, and disruptive/aggressive behavior), while the remaining seven items are graded on a 0–4 scale. These four items are given twice the weight of the others to compensate for poor cooperation from severely ill patients. The scale takes 15–30 min to complete. The scale is widely used by clinicians and researchers in the diagnosis, evaluation, and quantification of manic psychopathology.
The MINI-plus is a structured diagnostic interview, developed in 1990 by psychiatrists and clinicians in the United States and Europe for DSM-IV and ICD-10 psychiatric disorders. This scale is most widely used psychiatric structured diagnostic interview instrument in the world, employed by mental health professionals and health organizations all over the world.
The data collected were analyzed using frequency, mean, standard deviation for assessment of demographic variables. A Chi-square analysis was applied to identify the association between comorbid symptoms and polarity of first episode, polarity of last episode, age of onset, number of episodes, and duration of illness. The statistical analysis of the data was done by SPSS version 20.0 (IBM, Chicago, Illinois, USA).
| Results|| |
Out of the total of ninety participants, 60% were males (n = 54), whereas 40% were females (n = 36). Average age of the sample studies was 37.20 years ± 8.01 ranging from a minimum age of 18 years to maximum age of 50 years. Mean duration of illness was 12 years ± 7.3 years and the age at first onset of mood disorder was 25 years ± 5 years. For YMRS, the score for clinical remission was considered to be <7, and the mean score was 4.71. For HAM-D, the score for clinical remission was considered to be ≤7 and the mean score was 2.6 [Table 1].
|Table 1: Data regarding age, average monthly income, duration of illness (years), age at onset of first affective episode (years), number of manic episodes, number of depressive episodes, Young Mania Rating Scale score, Hamilton Depression Rating scale score|
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In terms of education, 40% of them had completed secondary education, followed by 23.3% having only completed primary education followed by college (18.9%) and then higher secondary (17.8%). More than half of the participants were married, one-fourth were single, 10% were living separate from their spouse, and 7% were divorced. Employment status of 43.3% (N = 39) was unemployed and one-fifth each were either involved in skilled or unskilled manual labor, 5.6% were students, whereas the rest were either involved in clerical jobs, were professionals, or were running their own businesses. Majority of the participants, that is, 60% belonged to nuclear family (N = 54), and 27 of them, that is, 30% were from a joint family and 10% belonged to extended families (N = 9).
Thirty-one percent patients had comorbid medical illness in the past, whereas 69% had no illness – most common being diabetes (14.4%, N = 13), and second most frequent being thyroid disorder and hypertension (5.5% each, N = 5), bronchial asthma (3.3%, N = 3), polycystic ovarian syndrome in 2 participants, and one each of dyslipidemia, simple tics, vocal nodules, and hydrocele.
Family history of BD was present in 17 out of the 90 subjects (18.8%), whereas alcohol and nicotine dependence was found in families of 10 participants each (11.1%), suicide in family of 5.5% patients, depressive disorders and psychosis in 3.3% each, and anxiety disorders in 2.2% [Table 2].
Based on the polarity of index episode, only 13.3% participants had depressive episode and the remaining had a manic episode as their first episode [Table 3]. With regard to the last episode, only 11% had depressive polarity, and 89% had mania as the polarity [Table 4].
|Table 3: Differences in psychiatric comorbid symptoms based on polarity of the first episode|
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|Table 4: Differences in psychiatric comorbid symptoms based on polarity of the last episode|
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Most common psychiatry comorbid symptom seen in BD was found to be drug dependence/abuse which was almost one-third around 34.4%, second most common at 23.3% being alcohol dependence/abuse (N = 21), followed by suicidality around 9% (N = 8), antisocial personality 6.3%, social phobia and panic disorder 4.4% each, and one patient who had agoraphobia.
On evaluation of polarity of first episode and comparing depressive and manic groups, only one condition – suicidality was found to be significant (P value of 0.04, x2 = 4.44). Twenty-five percent of patients with first episode depressive had suicidality versus only 6.4% of manic patients [Table 3].
Based on the polarity of last episode, on comparison of depressive and manic groups in relation to the parameter suicidality, there are eight participants who reported positive response. The number of positive responses is higher in depressive group (N = 5) than manic group (N = 3) with a percentage of 50. This comparison is statistically significant with a P < 0.001 (x2 = 23.48). On comparison of depressive and manic groups in relation to the parameter panic disorder, 3.8% had panic disorder in manic versus 10% in depressive group with a P value of 0.37 and was not significant. On comparison with respect to agoraphobia, there is only one participant with the disorder in the depressive group with none in the manic group, and this is statistically significant with a P value of 0.004 (x2 = 8.09). There are four participants who had positive responses for social phobia with 20% of participants in depressive group with social phobia and 2.5% in manic group. Statistically significant results were obtained with a P value of 0.011 and x2 = 6.41 [Table 4].
An arbitrary cutoff of more than 5 and <5 episodes showed no significance was found for any of the psychiatric symptoms [Table 5]. However, based on age of onset of first episode, suicidality was again found to be significant in age >40 years, as compared to younger age groups [Table 6].
|Table 5: Differences in psychiatric comorbid symptoms based on number of episodes (5 or less episodes and more than 5 episodes)|
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|Table 6: Differences based on age of onset (in years) of first affective episode|
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| Discussion|| |
Our study indicates that various psychiatric and medical comorbidities can be detected in bipolar patients who are in remission. The literature has long established a strong association between BD and substance abuse, anxiety disorders, attention-deficit/hyperactivity disorder, eating disorders, cyclothymia as well as other axis II personality disorders.
Based on the findings of Stanley foundation bipolar network, 65% had a comorbid diagnosis in BD. The division of the 65% was – 23% had one additional lifetime DSM-IV Axis I diagnosis, whereas18% had two additional lifetime Axis I diagnoses, and approximately one quarter (24%) had three or more such diagnoses. This 65% figure was in line with the observation from another study which reported that 60% of patients with BD admitted to psychiatric facilities had at least one other Axis I disorder.,
The most common psychiatric comorbidity was drug dependence. Thirty-four percent of patients had drug dependence/abuse and around 23% of patients were having alcohol dependence/abuse in our study. According to various studies, around 42% lifetime percentage of bipolar patients report substance use. This includes 33% of alcohol use, 16% use of marijuana, with stimulants and cocaine each present in 9% and sedatives, opiates and other hallucinogens contributing 8%, 7%, and 6%, respectively. According to another study, more than 60% patients had a lifetime substance use disorder. The findings in our study and previous studies were comparable.
In our study, we found that panic disorder, social phobia, and agoraphobia were more commonly seen in patients whose latest episode was depressive. Comorbidity with all anxiety disorders, with prevalence ranging from as high as 25% for panic disorder to as low as 3% for generalized anxiety disorder was detected in various studies. Social phobia was found in one study to have a prevalence of 16% and in another of 10%. In our study, we found the percentage of participants with comorbid panic disorder at 4%, social phobia at 4%, and agoraphobia at 1% which was lesser than that detected in other studies. Identifying anxiety spectrum disorders has treatment-related implications. A study by Hawke et al. with 204 participants of BD where 41% had comorbid anxiety disorders, scores suggestive of more severity in those with anxiety than those without were attained. Despite more severe illness characteristics, the treatment gains were equivalent or superior to that of the participants without anxiety disorders on a variety of outcome measures. Although the treatments were not specifically targeted toward anxiety disorder, the participants made significant improvements in anxiety symptoms. In the absence of any controlled trials in patients with comorbid bipolar and anxiety disorders, the initial goals of treatment should include mood stabilization and selection of those agents which have efficacy in the co-occurring anxiety disorder.
Suicidality was found to be significant for both age at onset of first episode and polarity of first episode with 25% of participants in depressive group indicating suicidality. It is estimated that 25% to 50% of patients with BD will attempt suicide at least once over their lifetime, and that 8% to 19% will complete suicide. Risk factors, according to one study, for suicide include younger age of onset of the illness, history of past suicidal acts, family history of suicide, and hopelessness, as well as comorbid borderline personality disorder and substance use disorders. The warning signs requiring immediate action include the patients threatening to harm themselves, or looking for access to pills or weapons or other means of self-harm, or the patient expressing about death by written or verbal modes. There is robust evidence supporting the effects of lithium treatment in reducing suicidal attempts and completions in BD.
The most common general medical comorbidities that are known to occur with BD are migraine, thyroid illness, obesity, type II diabetes, and cardiovascular disease. Our study indicates, 31% of patients had comorbid medical illness, most common being diabetes, and the second most frequent hypothyroidism. Although it is uncertain that medical disorders are truly comorbid, a consequence of treatment or their combination, medical disorders accompany BD at rates greater than predicted by chance.
Data suggest that very high proportion of patients with BD get married and marital rates are higher for patients with BD, when compared with those suffering from schizophrenia. In terms of divorce rates, studies suggest that patients with BD have higher rates of divorce. In terms of fertility rates, studies suggest that compared to those without the illness, the fertility rates among patients with BD are lower. In terms of marital adjustment, results are mixed with some studies suggesting poorer marital adjustment among patients and their spouses too.
Strengths and limitations
The study uses standardized tools used frequently in research. It analyses the impact of polarity of index and last episode on the comorbidity which has been studied in few studies. Factors such as comorbid medical conditions and current treatment details for psychiatric and medical condition were not analyzed for, which could confound results, example benzodiazepines which can confound the frequency of those with drug dependence, or patient receiving lithium which may reduce suicidality. Furthermore, the age of onset if earlier would also alter the average duration of years with illness. The sample size was small and not representative of the actual population due to convenience sampling technique and the reason why all psychiatric comorbid symptoms couldn't be obtained on interviews. The number of cases of depressive and manic episodes are variable and with fewer female samples than males, hence making the data less comparable.
A high index of suspicion should be maintained for developing a psychiatric comorbidity in high-risk groups. Early detection and management of psychiatric comorbidities in bipolar patients who are at risk may help in more holistic management. Change in management protocol for patients with comorbid substance use and anxiety symptoms should be considered. Further studies are required with larger sample size with emphasis on detecting the comorbidities to affirm the findings of the present study and to generalize the findings to a larger population.
| Conclusion|| |
Psychiatric comorbidities are a commonplace in bipolar disorder that may worsen its course and prognosis. Furthermore, comorbidities may need to be identified with proper scrutiny at follow-ups and appropriate interventions employed to prevent iatrogenic complications.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]