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Comorbidity Between Panic-Disorder and Bipolar Disorder Comorbidità Tra Disturbo Di Panico E Disturbo Bipolare

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Comorbidity Between Panic-Disorder and Bipolar Disorder Comorbidità Tra Disturbo Di Panico E Disturbo Bipolare Clinical psychopharmacotherapy • Psicofarmacoterapia clinica Comorbidity between panic-disorder and bipolar disorder Comorbidità tra disturbo di panico e disturbo bipolare G. Perugi*, C. Toni** * ** Department of Psychiatry, University of Pisa; * Institute of Behavioural Sciences “G. De Lisio”, Pisa Summary BPD, may divert the clinicians’ attention from the detection of The study of comorbidity between bipolar (BPD) and anxi- mood instability, thus diminishing the possibility of early and ety disorders (AD), and in particular panic/agoraphobic (PD) timely intervention. The empirical basis for therapeutic deci- disorder provides an opportunity to address important clinical sions remains largely inadequate. No firm recommendations and research questions. Epidemiological and clinical studies can be made as to which mood stabilizer is best for a BPD have documented the high lifetime rates and risks related to patient based on his/her particular co-morbid AD. Generally, BPD comorbidity in PD patients. This comorbidity is associ- the available data support the use of valproate as the mood sta- ated with several indices of severity such as early onset, mixed bilizer of choice for PD patients with comorbid BPD, especially presentations, severity of symptoms, poor symptomatic and in the presence of prominent anxiety symptoms, mixed features functional recovery, suicidal behaviour, diminished acute re- and/or rapid cycling. Antidepressants should be used with cau- tion and in combination with mood stabilizers. sponse to pharmacological treatment, decreased quality of life and an unfavourable course and outcome. The identification of the temporal sequence in comorbid BPD and AD may pro- Key words vide a refined view of the association between these comorbid Comorbidity • Bipolar disorder • Anxiety disorder • Panic/agoraphobic syndromes. Coexisting conditions, whose onset often precedes disorder Anxiety disorders (AD), and especially panic disorder quently associated with AD 3. Moreover, AD-BPD co- (PD), have been subject to different interpretative para- morbidity is associated with intensification of symptoms, digms. Until the end of the 20th century, all AD were con- increased risk of alcohol and drug abuse, inadequate ceived as part of the neurotic realm and the co-presence treatment response, pseudo-resistance, poor functional of anxiety with depression, phobic features and depend- outcome and suicidality 4-7. ent personality disorders was widespread brought within 1 the so-called general neurotic syndrome . Epidemiological and clinical data During the 1980s, the revaluation of the pharmacological dissection operated by D. Klein in the 1960s made PD out The reliability of lay interviewers diagnosing AD in com- of the realm of neuroses, challenging a switch of the current munity-based samples is well established, while the re- paradigm 2. Since that revolutionary breakthrough, PD was liability of identifying BPD cases with a predominantly treated essentially with tricyclic antidepressants for about mixed/dysphoric presentation is not ideal with the cur- 20 years. The introduction of serotonin reuptake inhibitors rently available diagnostic interviews 8 9. Clinical studies (SSRIs) at the end of the 1980s, and evidence of their anxi- indicate that AD comorbidity may be more prevalent in olytic efficacy, made the treatment of AD more feasible, mixed and “softer” expressions of BPD (or bipolar spec- even in primary care settings. Widespread confidence with trum) 10-12, suggesting that community-based epidemio- the use of SSRIs, at every level of care, has often led to logical studies may underestimate the prevalence of BPD underestimation of other psychopathological features as- comorbidity in AD subpopulations. sociated with AD, especially those of the soft bipolar spec- In the National Comorbidity Survey (NCS) (13, 14), the es- trum. Neglect of these latter manifestations may bring out timated lifetime prevalence of any AD in BPD was 92.9% several complications related to inadequate or incomplete (odds ratio, OR = 31.2). Specific phobia was the most treatment, from the risk of mood switch to the induction of prevalent AD comorbidity (66.6%), while PD was the mixed states (even if attenuated) or rapid cycling. least prevalent (33.1%). The reported risk of comorbid PD Epidemiological, clinical and familial studies provide is higher in BPD (OR = 11.0) compared to unipolar dis- compelling evidence that bipolar disorder (BPD) is fre- order (OR = 7.0). Two iterations of the NCS have shown Correspondence Giulio Perugi, Institute of Behavioural Sciences “G. De Lisio”, Pisa, Italy • E-mail: [email protected] • [email protected] Journal of Psychopathology 2012;18:75-81 75 G. Perugi, C. Toni that these data are reflective of the overall population in tively. Lifetime Axis I comorbidity was associated with the US and potentially for most other countries across the early age of onset of BPD symptoms, progressive sever- world 15. In a European sample, Angst et al. 16 reported ity of illness and a family history of alcoholism and drug higher rates of comorbidity with PD in subjects suffering abuse. Current anxiety comorbidity was also associated from DSM-IV hypomania, recurrent brief hypomania and with reduced occupational functioning, a history of rapid sporadic brief hypomania compared to population con- cycling and a shortening of well-being intervals. trols. More recently, in a European community sample, The prevalence of AD and its correlates was investigated Carta et al. 17 confirmed the strong relationship between in the first 500 patients (BPDI n = 360, BPDII n = 115) AD and soft expressions of BPD, quite often presenting as enrolled in the Systematic Treatment Enhancement Pro- subclinical depressive-anxious syndromes. gram for BPD (STEP-BPD) 5. The prevalence of any life- Concerning clinical studies, several investigations have time AD for the entire cohort was greater among patients reported on the prevalence of AD in patients with BPD. with BPD-I (51.2%) vs. BPD-II (30.5%). The age at onset Rihmer et al. 18 described the prevalence of AD comor- of BPD was significantly lower for patients with any life- bidity in 2953 primary care patients with a diagnosable time AD than in patients without AD (15.6 vs. 19.4 years, mood disorder. The estimated prevalence of any comor- respectively). Patients with a lifetime AD also had less bid AD was lowest among persons with BPD-I and high- education, shorter time of euthymia, lower rates of recov- est in the BPD-II patient group. The prevalence of comor- ery and elevated rates of lifetime suicide attempts. It was bid AD for the major depressive disorder group was inter- also reported that BPD with comorbid ADs had a higher mediate between the two BPD subgroups. This finding is prevalence of alcohol and substance use disorders. The consistent with the observation that softer expressions of presence of multiple ADs was independently associated BPD are often camouflaged as anxious depression in the with added impairment in quality of life and functioning. primary care setting 19 20. AD comorbidity in BPD has recently attracted consider- MacQueen et al. 21 reported that the prevalence of any AD able attention and has been reported to be widely repre- comorbidity in BPD was higher in sub-syndromal (80.6%) sented in BPD type II patients and predictive of a more than in the syndromal (54%) and euthymic (38.6%) phas- severe clinical picture and worse prognosis 6 7 24 25. es. In contrast, Dilsaver and Chen 22 reported that social The association between AD and alcohol and substance phobia (SoP) and PD presenting during a bipolar episode use disorders is an additional theme that is present in the were highly associated with suicidality, particularly in BPD literature. Bauer et al. 26 examined the prevalence and depressive phases. Recent observations have shown that the correlates of comorbid substance use disorders and AD in subjects presenting with (unipolar) depressive or AD in a sample of inpatients with BPD (n = 348). AD were an adequate screening for lifetime (hypo)-manic features associated with earlier age at onset, rapid cycling, higher can not only help the recognition of actual BPD, but also probability of reporting depressive symptoms, higher rates the identification of a subgroup of patients with more se- of prior suicide attempts, greater number of prior-year epi- vere symptomatology, more comorbid anxiety and alco- sodes, higher severity of illness scores and lower quality hol dependence disorders and more suicidality 12. of life. The negative effect of AD in BPD was particularly In this respect, it should be highlighted that panic attacks, evident in patients with BPD who also had a comorbid sub- anxiety and varying degrees of phobic avoidance, up to stance abuse disorder. Goodwin et al. 27 reported the asso- extended agoraphobia, are frequently reported also by ciation between AD and substance use disorders in BPD. In patients with cyclothymia 23. Panic attacks can be trig- particular, PD was associated with an increased prevalence gered by separation events or under the influence of cer- of cocaine, sedative and stimulant use disorders. tain substances such as stimulants or cannabis. In some More recently, data drawn from a controlled clinical cases, panic attacks start on the acme of periods of hyper- trial of acamprosate for subjects with BPD and alcohol activity or excitement, and sometimes mark the switch dependence showed that comorbid anxiety was pro- from an elated to a depressive phase 23. These observa- spectively associated with increased depressive symp- tions suggest that in some patients anxiety comorbidity is toms and alcohol use 28. Recent clinical studies on BPD most pronounced at the extremes of affective excursions, confirmed previous observations as far as earlier age at while in others, anxiety may present primarily as an ‘in- onset, higher number of episodes, suicidality, more se- terepisodic’ disturbance. vere illness course and impairment are concerned in pa- McElroy et al. 4 reported anxiety (n = 122, 42%) and sub- tients also suffering from AD 29 30.
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