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Bipolar Comorbidity: from Diagnostic Dilemmas to Therapeutic Challenge

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Bipolar Comorbidity: from Diagnostic Dilemmas to Therapeutic Challenge SECTION SPECIAL International Journal of Neuropsychopharmacology (2003), 6, 139–144. Copyright f 2003 CINP DOI: 10.1017/S1461145703003432 Bipolar comorbidity: from diagnostic dilemmas to therapeutic challenge Yehuda Sasson, Miriam Chopra, Eran Harrari, Keren Amitai and Joseph Zohar Chaim Sheba Medical Centre, Division of Psychiatry, Tel Hashomer, Israel Abstract Comorbidity in bipolar disorder is the rule rather than the exception – more than 60% of bipolar patients have a comorbid diagnosis – and is associated with a mixed affective or dysphoric state; high rates of suicidality; less favourable response to lithium and poorer overall outcome. There is convincing evidence Downloaded from https://academic.oup.com/ijnp/article/6/2/139/719859 by guest on 28 September 2021 that rates of substance use and anxiety disorders are higher among patients with bipolar disorder com- pared to their rates in the general population. The interaction between anxiety disorders and substance use goes both ways: patients with bipolar disorder have a higher rate of substance use and anxiety disorder, and vice versa. Bipolar disorder is also associated with borderline personality disorder and ADHD, and to a lesser extent with weight gain. As more than 40% of bipolar patients have anxiety disorder, it is indicated that while diagnosing bipolar patients, systematic enquiry about different anxiety disorders is called for. This also presents a therapeutic challenge, since agents that effectively treat anxiety disorders are associated with the risk of induced mania. Therefore, the treating psychiatrist needs to carefully evaluate the potential benefit of treating the anxiety against the potential cost of inducing a manic episode. A possible solution would be to use, when possible, a non-pharmacological intervention, such as a cognitive–behavioural approach. Alternately, it is suggested that the clinician attempts to ensure that the patient receives adequate treatment with mood stabilizers before slowly and carefully attempting the addition of anti-anxiety compounds with a relatively lower risk of mania induction (e.g. SSRIs compared to TCAs). Received 28 July 2002; Reviewed 13 November 2002; Revised 21 January 2003; Accepted 9 February 2003 Key words: Anxiety disorder, bipolar disorder, SSRIs, substance abuse. Introduction they are indeed independent, but this may not be entirely clear in, for example, depressive and anxiety Comorbidity has been defined as the presence of more disorders. than one disorder in a person, for a defined period of Another point to which close attention should be time (Wittchen, 1996). As the adherence to diagnosis paid is the different definitions being used; while according to diagnostic criteria has been widely ac- some studies use the ‘lifetime’ definition, others look cepted, comorbidity has by default become the rule, at the co-occurrence of two disorders. It is clear that rather than the exception (Van Praag, 1996). the prevalence of comorbidity is greater when the There are three main types of comorbidity: co- ‘lifetime’ definition is used. morbidity of physical and psychiatric disorders, e.g. The third methodological issue which should be depression and hyperthyroidism; comorbidity of taken into account is the population being studied. related disorders, e.g. anxiety and depression; and Population-based studies probably provide a better comorbidity of disorders indirectly related, e.g. estimation of comorbidity rates compared to studies psychotic depression and substance abuse. carried out in primary and secondary care settings, Methodological issues implicated in the research of which introduce the artifact of treatment-seeking into comorbidity include the question of whether the two the sample. The National Comorbidy Survey (NCS) of diagnoses being studied are truly independent of one the United States (Kessler et al., 1994) which docu- another. The current underlying hypothesis is that mented psychiatric diagnosis of over 8000 individuals in a population-based sample, is an example of a large population-based study. Address for correspondence: Professor J. Zohar, Chaim Sheba Medical Centre, Division of Psychiatry, Tel Hashomer, 52621, Israel. The last methodological issue is the base rate, i.e. the Tel.: 972 3 530 3300 Fax: 972 3 535 2788 chance that two disorders will occur concurrently is of E-mail: [email protected] course higher if the base rates of the two are high. 140 Y. Sasson et al. Thus, while weighing the significance of the co- Table 1. Axis I comorbidity in bipolar disordera morbidity, one also needs to take these base rates into account. Lifetime % (n) Current % (n) Comorbidity is usually associated with poorer prognosis and also may present a challenge for the None 101 (35) 67 (192) treating psychiatrist. For example, while treating one One or more 65 (187) 33 (96) condition (such as panic disorder) in patients with Two or more 42 (120) 13 (37) bipolar disorder, it might also lead to a hypomanic Three or more 24 (68) 6 (16) or even to a manic episode. Adapted from McElroy et al. (2001). However, theoretically comorbidity may advance a No difference in comorbidity between patients with our knowledge. For example, if two disorders fre- bipolar I and bipolar II disorders. quently coexist (e.g. depression and anxiety), this may shed some light on a possible common psychopatho- rate of eating disorders among patients with bipolar Downloaded from https://academic.oup.com/ijnp/article/6/2/139/719859 by guest on 28 September 2021 logical pathway, therefore providing an important disorder, while patients with eating disorders often lead for innovative research and therapeutic ap- have a higher prevalence of bipolar disorders (Halmi proaches [e.g. obsessive–compulsive disorder (OCD) et al., 1991; Simpson et al., 1992). and addiction]. As comorbidity is common in bipolar disorder Prevalence of bipolar comorbidity (McElroy et al., 2001) a number of questions often arise in this regard. The first relates to the rate of Based on the first 288 patients of the Stanley Foun- comorbid Axis I disorders across diagnostic subtypes dation Bipolar Network (SFBN) (McElroy et al., 2001), (e.g. bipolar I vs. bipolar II). The second is related to the 65% had a comorbid diagnosis. The breakdown of this effect of Axis I psychiatric comorbidity on phenomen- 65% is as follows: 23% had one additional lifetime ology, course, outcome and treatment response. This DSM-IV Axis I diagnosis, 18% had two additional paper will address these issues while reviewing the lifetime Axis I diagnoses, and approx. one quarter relevant literature on comorbidity in bipolar disorder. (24%) had three or more such diagnoses. This 65% figure is in line with the observation of Cassano et al. (1998) who reported that 60% of patients with bipolar Bipolar comorbidity disorder admitted to psychiatric facilities have at least There is convincing evidence that rates of substance one other Axis I disorder (see Table 1). use (Brady and Lydiard, 1992; Regier et al., 1990) and anxiety disorders (Chen and Dilsaver, 1995a,b) are Comorbidity of substance use with bipolar disorder higher among patients with bipolar disorder com- A fairly high lifetime percentage of bipolar patients pared to their rates in the general population. More- (42%) (McElroy et al., 2001) report on substance use. over, it appears that rates of substance use (Kessler This includes 33% of alcohol use, 16% use of mari- et al., 1996; Regier et al., 1990), panic disorder (Chen juana, with stimulants and cocaine each present in 9% and Dilsaver, 1995b) and OCD (Chen and Dilsaver, and sedatives, opiates and other hallucinogens con- 1995a) are higher in bipolar patients than in de- tributing 8, 7 and 6% correspondingly (see Table 2). pression patients. The interaction between anxiety Drug abuse is a significant indicator for the course disorders and substance use goes both ways: patients of bipolar disorder, not only with regard to the indi- with bipolar disorder have a higher rate of substance vidual but also in relation to family history of drug use and anxiety disorder, and vice versa; patients with abuse. In a logistic regression carried out by McElroy substance use and anxiety disorders often have bi- et al. (2001) a family history of drug abuse was found polar disorder (Bowen et al., 1995; Brady and Lydiard, to be one of three factors which provided a signifi- 1992; Sonne et al., 1994). cant indicator for lifetime comorbid Axis I disorders Bipolar disorder is associated with borderline per- in patients with bipolar disorder. The other two sonality disorder (Pinto and Akiskal, 1998) and ADHD indicators were early onset of bipolar disorder and (Faraone et al., 1997; Geller et al., 1998). It also has early onset of affective symptoms. been linked with weight gain (Elmslie et al., 2000). However, the comorbidity of bipolar and eating Comorbidity of bipolar and anxiety disorders disorders is less prominent (Kruger et al., 1995; Strakowski et al., 1992, 1993, 1994), yet the interaction The prevalence rate of comorbid bipolar and anxiety between them also goes both ways: there is a higher disorders is similar to that in substance use, i.e. a 42% Bipolar comorbidity 141 Table 2. Comorbidity of substance use disorders with bipolar Table 3. Comorbidity of anxiety disorders with bipolar disorder disorder Lifetime % (n) Current % (n) Lifetime % (n) Current % (n) Substance use disorders 42 (122) 4 (12) Anxiety disorders 42 (122) 30 (66) Alcohol 33 (96) 2 (7) Panic disorder/agoraphobia 20 (58) 9 (27) Marijuana 16 (45) 3 (8) Social phobia 16 (47) 13 (36) Stimulant 9 (25) 0 (1) Simple phobia 10 (30) 8 (24) Cocaine 9 (27) 1 (2) OCD 9 (27) 8 (22) Sedative 8 (24) 0 (1) PTSD 7 (19) 4 (12) Opiate 7 (20) 0 (1) Generalized anxiety disorder 3 (8) 3 (8) Hallucinogen 6 (18) 0 (1) Other anxiety disorders 3 (8) 2 (6) Downloaded from https://academic.oup.com/ijnp/article/6/2/139/719859 by guest on 28 September 2021 Adapted from McElroy et al.
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