Int J Psychiatry Clin Pract 2014; 18: 248–254. © 2014 Informa Healthcare ISSN 1365-1501 print/ISSN 1471-1788 online. DOI: 10.3109/13651501.2014.959972
ORIGINAL ARTICLE
Prevalence and disability of comorbid social phobia and obsessive–compulsive disorder in patients with panic disorder and generalized anxiety disorder
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Giulia Camuri§, Lucio Oldani§, Bernardo Dell’Osso, Beatrice Benatti, Licia Lietti, Carlotta Palazzo & A. Carlo Altamura
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Department of Neuroscience and Mental Health, University of Milan, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy Abstract Objective. Generalized anxiety disorder (GAD) and panic disorder (PD) are disabling conditions, often comorbid with other anxiety disorders. The present study was aimed to assess prevalence and related disability of comorbid social phobia (SP) and obsessive–compulsive disorder (OCD) in 115 patients with GAD (57) or PD (58). Methods. Patients were classified as having threshold, subthreshold, or no comorbidity, and related prevalence rates, as well as disability (Sheehan Disability Scale, SDS), were compared across diagnostic subgroups. Results. SP and OCD comorbidities were present in 30.4% of the sample, with subthreshold comorbidities present at twice the rate of threshold ones (22.6% vs. 11.3%). Compared with GAD patients, PD patients showed significantly higher subthreshold and threshold comorbidity rates (27.6% and 13.8% vs. 17.5% and 8.8%, respectively). Comorbid PD patients had higher SDS scores than the comorbid and non-comorbid GAD subjects. The presence of threshold SP comorbidity was associated with the highest SDS scores. Conclusions. SP and OCD comorbidities were found to be prevalent and disabling among GAD and PD patients, with higher subthreshold than threshold rates, and a negative impact on quality of life. Present findings stress the importance of a dimensional approach to anxiety disorders, the presence of threshold and subthreshold comorbidity being the rule rather than the exception. Key words: Anxiety disorders, generalized anxiety disorder, panic disorder, subthreshold comorbidity, threshold comorbidity, disability (Received 15 November 2013; accepted 22 August 2014)
Introduction Anxiety disorders are common, comorbid, and disabling conditions, with a lifetime prevalence of approximately 17% in the general population (Baldwin et al. 2010). Among such conditions, generalized anxiety disorder (GAD) and panic disorder (PD) are the most common disorders, with a prevalence of 1.7–3.4% and 1.8%, respectively (Wittchen et al. 2011). In particular, disability related to anxiety disorders is responsible for both economic and human burden, particularly in terms of social and occupational functioning, perceived emotional and physical health, as well as daily life satisfaction (Graystone et al. 2009; Kertz and Woodruff-Borden 2011). Anxiety disorders generally show high rates of psychiatric comorbidities, either as threshold or subthreshold manifestations, and the presence of one disorder seems to increase §
Equally contributing first author. Correspondence: Dott. Bernardo Dell’Osso, Department of Neuroscience and Mental Health, University of Milan, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano, Italy. Tel: ⫹ 02-55035994. Fax: ⫹ 02-50320310. E-mail: [email protected]
the probability of having an additional one (Nutt and Ballenger 2003). In fact, the use of a dimensional diagnostic approach, rather than a categorical one, was found to allow a more accurate assessment of subthreshold comorbidity and overall complexity of more severe clinical pictures, in order to establish optimal treatments (Angst et al. 2004, 2009). For instance, a recent study found that individuals with a previous anxiety disorder and current subthreshold anxiety had a greater risk of suffering from subsequent episodes (Kertz and Woodruff-Borden 2011). Therefore, the assessment of subthreshold anxiety represents a crucial step in targeting patients, who might benefit from early interventions and preventive measures (Meulenbeek et al. 2010). Indeed, a recent article by Karsten and colleagues found that the presence of subthreshold anxiety or a prior history of a specific anxiety disorder predicted the disorder recurrence within 2 years, with the highest risk for those who had suffered from both (Karsten et al. 2011). Of note, a recent study reported a 50.6% rate of psychiatric comorbidity in PD, 12.4% of which was represented by subthreshold conditions (Oral et al. 2012). Furthermore, a study focused on subthreshold symptoms in PD found that, after one year of follow-up, threshold comorbidity decreased,
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DOI: 10.3109/13651501.2014.959972
whereas subthreshold comorbidity increased. In addition, panic symptoms’ severity decreased, whereas subthreshold PD continued to be present and disabling (Karsten et al. 2011). With respect to GAD, current literature shows high levels of psychiatric comorbidity with negative influence on prognosis and quality of life (Angst et al. 2009). In particular, a recent article conducted by Blanco and colleagues found that the prevalence of GAD patients, with at least one psychiatric comorbidity, was up to 90.2%. Comorbidity was represented by mood and anxiety disorders, personality disorders, pathological gambling, and substance abuse (Blanco et al. 2014). Among comorbid anxiety disorders, social phobia (SP) and obsessive–compulsive disorder (OCD) are frequently observed as co-occurring conditions (Wittchen et al. 2000). In particular, different authors have proposed a dimensional approach to SP, conceptualizing the disorder within a continuum of symptom severity, distress, degree of avoidance and impairment, including subthreshold presentation in such classification (Stein et al. 2000; Merikangas et al. 2002). Fehm and colleagues, in turn, identified two other conditions characterized by social anxiety, besides threshold SP, which did not fulfill all criteria of the Dianostic and Statystical Manual of Mental Disorders (DSM): 1) subthreshold presentation, meeting criterion A for DSM, without satisfying the other criterion and 2) symptomatic conditions, characterized by strong social fears, without meeting two or more DSM criteria (Fehm et al. 2008). One of the earliest studies focused on SP spectrum found a link between subclinical presentation and work attendance problems, poor grades in school, conduct disturbances, impaired subjective social support, lack of self-confidence and close friends, use of psychotropic compounds, as well as a greater number of negative life events, chronic medical problems, and mental health visits (Davidson et al. 1994). With respect to OCD, it should be taken into consideration that many subjects with obsessions and/or compulsions might not be diagnosed with OCD (according to DSM criteria), in spite of frequently presenting consequences which are similar to those in patients with threshold OCD, such as reduced quality of life and impaired functioning (De Bruijn et al. 2010). Fineberg and colleagues recently investigated the prevalence and clinical consequences of psychiatric comorbidity in both threshold and subclinical OCD, reporting a high prevalence of mood and anxiety disorders. Authors showed how psychiatric comorbidity rates increased with growing OCD severity (from both subclinical to full syndromes) and negatively impacted patients’ quality of life (Fineberg et al. 2013). More recently, Adam and co-workers found that patients with subthreshold OCD had an increased risk for psychiatric comorbidity, significant daily life impairment, and health care utilization (Adam et al. 2012). The aforementioned studies stress the importance of assessing comorbid subthreshold symptoms as well as threshold conditions in patients with anxiety disorders. Therefore, the aim of the present study was to analyze and compare comorbid (i.e., subthreshold and threshold) SP and OCD, as well as related disability, in a sample of patients primarily suffering from GAD and PD.
Subthreshold comorbidity and disability 249 Methods Study sample included 115 consecutive outpatients, attending the University Department of Psychiatry of the Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico of Milan, recruited in the period between January 2008 and January 2013, who were cross-sectionally evaluated. Subjects were predominantly citizens living in different city areas, of either gender, aged 18 years and older. To be enrolled in the study, patients were requested to have a primary diagnosis of GAD (n ⫽ 57) or PD (n ⫽ 58), according to DSM-IV-TR criteria (American Psychiatric Association 2000). In fact, patients were excluded when they did not meet GAD or PD criteria as primary diagnoses. No further exclusion criteria were considered; therefore, no patient was excluded from the original sample. After obtaining written informed consent from patients to have their personal records reviewed for research purposes, different socio-demographic and clinical variables (i.e., age at onset, age at first treatment, education level, family history for psychiatric disorders, psychiatric and medical comorbidity, etc.) were collected. In particular, the presence of any comorbid condition (i.e., threshold and subthreshold) was assessed through the SCID-I (First et al. 2002), along with the administration of specific psychometric scales. In particular, in order to evaluate and quantify symptom severity, identify subthreshold anxiety symptoms, and assess disability, the following psychometric scales were administered: Sheehan Disability Scale (SDS) (Sheehan et al. 1996), Liebowitz Social Anxiety Scale (LSAS) (Liebowitz 1987), Yale–Brown Obsessive Compulsive Scale (Y-BOCS) (Goodman et al. 1989a, 1989b), and Panic and Agoraphobia Scale (PAS) (Bandelow 1995). With respect to the PAS, patients were considered to have agoraphobia when they had selected four or more feared/avoided situations in the given list. Due to the lack of uniform consensus on subthreshold SP and OCD definition, they were classified using double criteria: clinical interview and psychometric scales. Therefore, for the purpose of the study, when criteria for full syndromal disorders (i.e., clinical conditions above the diagnostic threshold) were not satisfied at the Structured Clinical Interview for DSM IV Axis I Disorders (SCID-I), in order to qualify as subclinical manifestations, the following cutoff values were established, based on psychometric evaluation (i.e., LSAS and Y-BOCS): subthreshold SP defined as 25 ⱕ LSAS ⱕ 55 and subthreshold OCD defined as 7 ⱕ Y-BOCS ⱕ 15. With respect to subthreshold SP, due to the lack of uniform consensus for the lowest cut-off at the LSAS, we referred to the median value of the sample to set such threshold. With respect to subclinical OCD, according to available literature, a Y-BOCS range between 7 and 15 was identified for such purpose (Federici et al. 2010; Albert et al. 2001). Descriptive and comparative statistical analyses across subgroups (in terms of diagnosis, GAD vs. PD; type of comorbidity, SP vs. OCD) were performed using Student’s t-test for continuous variables and chi-square test for the dichotomous ones (SPSS version 20). Comorbidity rate comparisons were performed considering any comorbidity (threshold ⫹ subthreshold), threshold, and subthreshold separately. The same approach was used for comparing disability levels,
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including non-comorbid cases as well. When evaluating differences across subgroups in terms of pharmacotherapy (mono- vs. poly-therapy), the association of benzodiazepines with other therapies was not considered as an additional treatment. The administered psychometric questionnaires were part of the routine assessment carried out in the out-patients unit of our Department. Since this study had no experimental procedure, set on a purely observational design, no specific Ethical Committee approval was required. Results Main socio-demographic and clinical features of study sample and related subgroups are listed in Table I. The total sample showed a mean age of 45.16 ⫾ 15.43 (GAD, 51.53 ⫾ 15.17 and PD, 38.79 ⫾ 12.95) years, a male/female ratio of approximately 1:2 (total sample 32.2% vs. 67.8%; GAD 31.6% vs. 68.4%; PD 32.8% vs. 67.2%) and a graduation rate of 21.2% (24.6% in GAD vs. 17.9% in PD). A positive family history for psychiatric disorders was observed in 72.6% of the sample, without any significant difference across groups. A mean duration of untreated illness (DUI) of 4 years (47.32 ⫾ 75.19 months) was found for the total sample, with a longer DUI in GAD than that in PD, though not statistically significant (GAD 54.79 ⫾ 80.02 months vs. PD 40.13 ⫾ 70.2 months) (Table I). With respect to age at onset, GAD patients showed a significantly later onset (38.14 ⫾ 14.54 years in GAD vs. 30.40 ⫾ 13.26 years in PD patients; t ⫽ 2.97; p ⫽ 0.004) (Table I). When assessing the age at onset, it was found that patients with any comorbidity (subthreshold or threshold OCD or SP) showed an earlier age at onset than the non-comorbid patients (29.29 ⫾ 12.92 years vs. 36.49 ⫾ 14.51 years; t ⫽ 2.49; p ⫽ 0.014). Such result was not confirmed when considering only subclinical presentations. With respect to pharmacotherapy, the use of poly-therapy, observed in 39.5% of the total sample, was found to be significantly more frequent in GAD versus PD patients (56.1% vs. 22.8%, respectively; χ2 ⫽ 13.25; p ⬍ 0.001). Table I. Main socio-demographic and clinical variables of the study sample. Total sample (n ⫽ 115) Age at onset (years)* DUI (months) Subthreshold SP Subthreshold OCD Any subthreshold Threshold SP Threshold OCD Any threshold Any comorbidity
34.33 ⫾ 14.38
GAD patients (n ⫽ 57) 38.14 14.54*
47.32 ⫾ 75.19 54.79 ⫾ 80.02 16.5% (n ⫽ 19) 15.8% (n ⫽ 9) 7.8% (n ⫽ 9) 3.5% (n ⫽ 2)
PD patients (n ⫽ 58) 30.40 13.26* 40.13 ⫾ 70.20 17.2% (n ⫽ 10) 12.1% (n ⫽ 7)
22.6% (n ⫽ 26) 17.5% (n ⫽ 10) 27.6% (n ⫽ 16) 8.7% (n ⫽ 10) 3.5%§ (n ⫽ 2) 13.8%§ (n ⫽ 8) 4.3% (n ⫽ 5) 7.0% (n ⫽ 4) 1.7% (n ⫽ 1) 11.3% (n ⫽ 13) 8.8% (n ⫽ 5) 13.8% (n ⫽ 8) 30.4% (n ⫽ 35) 21.0%^ (n ⫽ 12) 39.7%^ (n ⫽ 23)
GAD, generalized anxiety disorder; SP, social phobia; OCD, obsessive– compulsive disorder; DUI, duration of untreated illness. *p ⫽ 0.004, t ⫽ 2.97. § p ⫽ 0.05, χ2 ⫽ 3.71. ^ p ⫽ 0.03, χ2 ⫽ 4.69. Bold values are statistically significant.
When considering the presence of any comorbidity (threshold and subthreshold SP and OCD), 30.4% of the total sample was found to have comorbidity, with statistically higher rates in PD than those in GAD (39.7% vs. 21.0%, respectively; χ2 ⫽ 4.69; p ⫽ 0.03) (Table I). Threshold comorbid conditions were less frequent (11.3%) than subclinical ones (22.6%) in the total sample, the first being distributed as follows: 8.7% for SP in the total sample (3.5% in GAD and 13.8% in PD patients) and 4.3% for OCD in the total sample (7% in GAD and 1.7% in PD patients) (Table I). The 16.5% of the total sample met criteria for subthreshold SP, without any significant difference between diagnostic groups (15.8% in GAD and 17.2% in PD patients). In comparison with SP, a lower rate of subthreshold OCD was observed in the whole sample (7.8%), with higher rate for PD in comparison with GAD patients (12.1% vs. 3.5%, respectively). With respect to the presence of “agoraphobia,” 71.7% of PD patients showed such condition, as recorded through the PAAS, considering those fearing/avoiding more than four situations as agoraphobic patients. In particular, 47.4% of the patients with agoraphobia and 33.3% of those without it presented at least one of the aforementioned comorbidities. With respect to comorbidity subtypes, PD patients with agoraphobia showed the following percentages when compared with PD patients without agoraphobia: 18.4% versus 20%, subclinical SP; 13.1% versus 13.3%, subclinical OCD; 18.4% versus 6.6%, threshold SP; and 2.6% versus 6.6%, threshold OCD. The comparison between these subgroups did not show any significant difference from a statistical point of view. In terms of disability, the total score and, more specifically, the three major items of the SDS (family, relationship, and work) were analyzed across different subgroups as follows: non-comorbid versus comorbid GAD and PD patients, subthreshold SP versus threshold SP, and subthreshold OCD versus threshold OCD. Related results are summarized in Table II and graphically presented in Figure 1. PD patients did not show statistically significant differences in comparison with GAD patients, when the overall level of disability was analyzed. However, higher disability levels, in terms of SDS total score and social functioning item, were found in comorbid compared with those in non-comorbid conditions, both in the total sample and in PD patients (total sample: t ⫽ ⫺ 2.10, p ⫽ 0.027 and t ⫽ ⫺ 3.24, p ⫽ 0.002, respectively; PD: t ⫽ ⫺ 2.56, p ⫽ 0.007 and t ⫽ ⫺ 3.07, p ⫽ 0.001, respectively). In terms of SP, significant differences were observed in terms of work disability in the total sample and in GAD patients, full syndromes being more disabling than subclinical ones (total sample: t ⫽ ⫺ 2.75, p ⫽ 0.005; GAD: t ⫽ ⫺ 2.16, p ⫽ 0.001). No significant differences were found when considering OCD comorbidities (Table II). Finally, when evaluating whether patients with any subthreshold condition, regardless of its nature (SP or OCD), had higher disability than non-comorbid patients, they were found to show a higher degree of impairment according to the social item of the SDS (t ⫽ ⫺ 3.04, p ⫽ 0.003). When the same analysis was performed across the diagnostic subgroups, no statistical significance or trend was observed.
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Table II. Disability level (evaluated through the SDS) of the study sample, according to subthreshold and threshold symptoms.
Total sample (n ⫽ 115) Non-comorbid patients (n ⫽ 80) Patients with any comorbidity (n ⫽ 35) Patients with any subthreshold (n ⫽ 26) Patients with any threshold (n ⫽ 13) Total sample with subthreshold SP (n ⫽ 19) Total sample with threshold SP (n ⫽ 10) Total sample with subthreshold OCD (n ⫽ 9) Total sample with threshold OCD (n ⫽ 6) PD patients (n ⫽ 58) PD patients with no comorbidity (n ⫽ 35) PD patients with any comorbidity (n ⫽ 23) PD patients with any subthreshold (n ⫽ 16) PD patients with any threshold (n ⫽ 8) PD patients with subthreshold SP (n ⫽ 10) PD patients with threshold SP (n ⫽ 8) PD patients with subthreshold OCD (n ⫽ 7) PD patients with threshold OCD (n ⫽ 2) GAD patients (n ⫽ 57) GAD patients with no comorbidity (n ⫽ 45) GAD patients with any comorbidity (n ⫽ 12) GAD patients with any subthreshold (n ⫽ 10) GAD patients with any threshold (n ⫽ 5) GAD patients with subthreshold SP (n ⫽ 9) GAD patients with threshold SP (n ⫽ 2) GAD patients with subthreshold OCD (n ⫽ 2) GAD patients with threshold OCD (n ⫽ 4)
Social disability (mean ⫾ SD)
Familiar disability (mean ⫾ SD)
Work disability (mean ⫾ SD)
Disability: total score
6.3 ⫾ 2.9 5.55 3.18* 7.28 2.53* 7.23 ⫾ 2.16 8.75 ⫾ 2.00 6.84 ⫾ 2.29 8.50 ⫾ 2.12 7.78 ⫾ 1.86 7.16 ⫾ 4.49 6.42 ⫾ 3.01 5.25 3.47^ 7.69 1.96^ 7.50 ⫾ 1.78 8.38 ⫾ 2.32 7.00 ⫾ 1.82 8.37 ⫾ 2.32 8.28 ⫾ 1.38 6.50 ⫾ 4.95 6.17 ⫾ 2.82 5.66 ⫾ 3.03 6.05 ⫾ 3.31 6.80 ⫾ 2.70 9.50 ⫾ 1.00 6.66 ⫾ 2.82 9.00 ⫾ 1.41 6 ⫾ 2.82 7.5 ⫾ 5.0
4.87 ⫾ 3.0 4.70 ⫾ 3.24 5.24 ⫾ 2.41 5.35 ⫾ 2.27 5.75 ⫾ 2.89 5.47 ⫾ 2.09 5.10 ⫾ 2.68 5.00 ⫾ 2.91 4.83 ⫾ 4.00 4.77 ⫾ 3.04 4.31 ⫾ 3.48 5.26 ⫾ 2.26 5.12 ⫾ 2.27 5.50 ⫾ 2.20 5.40 ⫾ 1.84 5.50 ⫾ 2.20 5.14 ⫾ 3.02 5.50 ⫾ 3.53 4.96 ⫾ 3.02 4.68 ⫾ 3.19 4.75 ⫾ 3.07 5.70 ⫾ 2.35 6.25 ⫾ 4.34 5.55 ⫾ 2.45 3.50 ⫾ 4.94 4.5 ⫾ 3.53 4.50 ⫾ 5.26
5.53 ⫾ 3.1 5.36 ⫾ 3.19 5.91 ⫾ 2.98 5.35 ⫾ 3.01 7.67 ⫾ 2.29 4.68 3.07§§ 7.70 2.16§§ 6.33 ⫾ 3.00 6.66 ⫾ 4.08 5.62 ⫾ 3.11 4.74 ⫾ 3.66 6.22 ⫾ 2.39 5.69 ⫾ 2.41 7.13 ⫾ 2.03 5.10 ⫾ 2.60 7.12 ⫾ 2.03 6.71 ⫾ 1.70 7.50 ⫾ 3.53 5.44 ⫾ 3.1 5.0 ⫾ 3.23 4.83 ⫾ 4.10 4.80 ⫾ 3.88 8.75 ⫾ 2.50 4.22 3.63°° 10 0.00°° 5 ⫾ 7.07 6.25 ⫾ 4.78
15.92 ⫾ 7.69 14.88 7.93° 18.11 6.65° 17.92 ⫾ 6.0 20.46 ⫾ 7.89 17.00 ⫾ 6.09 21.30 ⫾ 4.99 19.11 ⫾ 6.83 18.67 ⫾ 11.34 16.33 ⫾ 7.46 14.30 8.15§ 19.17 5.08§ 18.31 ⫾ 4.64 21.0 ⫾ 5.45 17.50 ⫾ 4.17 21.0 ⫾ 5.45 20.14 ⫾ 5.14 19.50 ⫾ 12.02 15.51 ⫾ 7.97 15.35 ⫾ 7.81 16.08 ⫾ 8.84 17.30 ⫾ 7.92 19.60 ⫾ 11.54 16.44 ⫾ 7.95 22.50 ⫾ 3.53 15.50 ⫾ 13.43 18.25 ⫾ 12.86
SDS, Sheehan Disability Scale; SD, standard deviation; SP, social phobia; OCD, obsessive–compulsive disorder; PD, panic disorder; GAD, generalized anxiety disorder Bold values are statistically significant..
Discussion Results from the present study suggest that anxiety disorders may frequently show mixed presentation with different symptoms belonging to a common spectrum. In fact, onethird of the total sample showed some degree of comorbidity (threshold or subthreshold). In such perspective, our findings, in relation to general comorbidity, are relevant because almost one-third of the total sample showed some degree of comorbidity, whereas about 70% of patients showed no comorbidity. In addition, the condition of agoraphobia was found to be present in about two-thirds of the patients affected by PD, indicating that the presence of significant agoraphobia (ⱖ 4 items at the PAAS) was associated with the presence of any comorbidity. However, it needs to be stressed that assessed comorbidity was related only to SP and OCD, and it is likely that screening for other anxiety and non-anxiety comorbidities would have given higher rates. With respect to comorbid cases, a higher prevalence of subthreshold disorders, than that of threshold ones, was found for the total sample and subgroups of patients with GAD and PD. In addition, a higher prevalence of subthreshold comorbid conditions was observed in PD than in GAD patients. The presence of subthreshold comorbidity was about twice as frequent in PD as in GAD patients (27.6% vs. 17.5%). In particular, a similar distribution of subthreshold SP was found between the two conditions (17.2% vs. 15.8%), whereas subthreshold OCD was about three
times more frequent in patients affected by PD than GAD (12.1% vs. 3.5%). Such result might be partially explained considering the frequency of hypochondriac symptoms reported by patients with PD. Hypochondriasis, in fact, is a frequent symptom observed in such patients; being a multidimensional syndrome, PD is characterized by the persistent fear of having a serious illness, based on misinterpretation of somatic sensations (Greeven et al. 2006). Similarities between hypochondriasis, obsessive–compulsive and panic symptoms, in terms of phenomenological presentation, have been reported in literature (Abramowitz 2005). The frequent misinterpretation of body sensations, encountered in PD patients, might lead to the development of obsessive beliefs regarding one’s health and ritualistic checking behaviors of one’s general body functions (e.g., checking heart beat subsequent to tachycardia) (Longley et al. 2010). Of note, threshold comorbidities were less frequent than subclinical presentations in the total sample, with higher percentage of OCD in GAD (7.0% vs. 1.7%) and SP in PD patients (13.8% vs. 3.5%). Taken as a whole, such results stress the importance of detecting subthreshold comorbid conditions in anxiety disorders as well as threshold ones, and investigating their onset within the course of illness. A shorter, although not statistically significant, DUI in PD versus GAD patients (on average, 14 months) can be
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25 22,5 21,3
20
19,11 18,67
18,11°
21 19,17
18,25 17,5
17
15
14,88°
20,14 19,5
§
16,44 16,08 15,35 14,3
15,5
Non comorbid patients
§
Patients with any comorbidity Subthreshold SP
10 Threshold SP
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Subthreshold OCD 5 Threshold OCD
0 Total sample
PD
GAD
Figure 1. Graphical explanation of the content of last column in Table II. The total mean Sheehan Disability Scale scores are shown for the comorbidity subgroups (no comorbidities vs. any comorbidities and threshold vs. subthreshold SP/OCD), in the total sample and within the single disorders (PD and GAD). Statistics: °p ⫽ 0.027, t ⫽ ⫺ 2.10, F ⫽ 3.15. §p ⫽ 0.007, t ⫽ ⫺ 2.56, F ⫽ 9.36.
explained considering a generally more acute onset with disabling physical symptoms in PD, leading patients to seek help earlier than GAD subjects, who often show an insidious and more gradual onset (Dell’Osso et al. 2013; Altamura et al. 2010a, 2010b). Another interesting finding is represented by the earlier age of onset in patients with comorbidity (either subthreshold or threshold) versus non-comorbid cases (on average, 7 years earlier). It has already been noticed that early-onset cases of GAD show a higher degree of comorbidity (including social phobia and substance abuse) (Chou 2009), as reported for PD subjects as well (Katerndahl and Talamantes 2000). Such findings remark the need for an early assessment of patients with any comorbid condition belonging to the entire anxiety spectrum, as an earlier age at onset may correlate with a more severe course (e.g., having more comorbidity) and a worse clinical outcome (Gonçalves and Byrne 2012; Le Roux et al. 2005; Goodwin and Hamilton 2002). With respect to disability, it was observed both in the total sample and in PD patients that the presence of any comorbidity negatively influenced the overall individual and social functioning, in particular. This finding might be expected, since SP and OCD, when present either as threshold or subthreshold conditions, can impair both psychosocial and relational skills (Wittchen et al. 2000; Wittchen and Fehm 2001). A similar result was observed for the GAD group, although differences in terms of disability between patients with and without comorbidity were not statistically significant (p ⫽ 0.54 for overall disability; p ⫽ 0.14 for social disability). Indeed, such discordance might indicate a specifically higher disability for PD patients, but should be interpreted cautiously, considering the limited size of the sample.
Another noteworthy finding is represented by the higher social disability, compared with the familial and occupational one, observed for the overall sample and related subgroups (GAD and PD). Apparently, patients with a disorder belon-ging to the anxiety spectrum showed a more severe deficit in social functioning, while occupational and familial areas, in particular, appeared to be less impaired. Such finding might be explained considering that situations eliciting social skills are, often, the first to be avoided by patients affected by anxiety disorders. On the other hand, family represents a protective environment for them, who usually tend to seek domestic shelter and familial reassurance (Rector et al. 2011). Another interesting result was represented by the higher work disability associated with threshold SP versus subclinical SP, both in the total sample and in GAD. From this perspective, there is evidence from literature that SP impairs work and social life more than family life (Wittchen et al., 2000). Several authors, in fact, have shown that individuals affected by this condition tend to be more financially dependent, more frequently underemployed, less productive at work, and underpaid, when compared with non-affected subjects (Wittchen et al., 2000; Schneier et al., 1992; Stein et al., 2000). The varying presence of poly-therapy across diagnostic groups, with a higher rate in GAD versus PD patients (56.1% vs. 22.80%, respectively; p ⬍ 0.001), is worthy of comment. This may be explained by the different clinical presentations of the disorders. GAD, in particular, can determine a polymorphic syndrome with a frequent chronic course, characterized by several symptoms, including sleep disturbance and physical complaints like fatigue, muscle tension, restlessness, and
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DOI: 10.3109/13651501.2014.959972
migraine. Such conditions may require additional treatment, such as low doses of atypical antipsychotics and pregabalin, which represent well-established, non-antidepressant treatments used for the management of GAD patients (Kavan et al. 2009; Zahreddine and Richa 2013; Mellman 2006). On the other hand, PD tends to generate a more acute and definite clinical picture, with frequent but short-lasting somatic complaints, as well as less frequent insomnia, than GAD (Ohayon et al. 1998). However, it should be acknowledged that the use of benzodiazepines was not considered as a poly-therapy, and it may be possible that, in such perspective, PD patients may have shown differences other than those the GAD subjects. Nevertheless, we cannot exclude the possibility that a higher prevalence of poly-therapy, administered for other reasons (e.g., major severity of illness), has somehow influenced prevalence rates of comorbid conditions and related disability. In the context of the reported results, the following limitations should be taken into account. First, present findings are conditioned by the limited sample size, particularly for the assessment of both subthreshold and threshold comorbidities. In this perspective, some non-significant results might be due to type 2 error. Furthermore, the naturalistic way of collecting data entailed the reliability of patients and avai-lable family members: consequently, information may not always be precise. Moreover, the fact that patients with subclinical SP and OCD had higher disability should encou-rage extending the analysis of comorbidity to other anxiety disorders and all affective area, in particular to subclinical depression. From this perspective, a recent article published by Karsten and colleagues showed that the occurrence of anxiety disorders was best predicted by a combination of history of anxiety disorder and subthreshold anxiety, closely followed by a combination of history of depressive disorder and subthreshold depression (Karsten et al. 2011). Finally, as previously pointed out, it should be considered that current pharmacological treatments may have influenced prevalence rates of comorbid conditions as well as related disability, likely underestimating the phenomenon, compared to drug naïve/free patients. In conclusion, present findings indicate a higher prevalence of subthreshold versus threshold OCD and SP comorbidity in patients with GAD and PD, showing significant consequences on patients’ functioning and quality of life and, finally, stressing the importance of assessing subclinical in addition to full syndromal manifestations. Such aspects represent a relevant field of clinical interest and a potential resource for efficiently targeting subjects at risk, who might benefit most from both psychotherapy and early pharmacological intervention strategies. Nevertheless, the inclusion of subclinical presentations into clinical practice assessment needs to be considered with caution, in order to not overpathologize physiological anxiety, such as temperamental shyness and perfectionism, belonging to normal rates of the emotional spectrum. From such perspective, proper and standardized criteria with uniform consensus on specific psychometric scales’ cut-off need to be further investigated.
Key points • • • • •
GAD and PD are potentially disabling disorders, which show high rates of comorbid anxiety both at threshold and subthreshold levels. PD patients show higher subthreshold and threshold comorbidity, particularly in terms of SP. High degree of comorbidity correlates with more severe impairment in the overall quality of life and, particularly, in the social functioning. Within the considered comorbidity spectrum, threshold SP resulted in the most impairing condition. Higher rates of poly-therapy were found in GAD patients when compared with those in PD patients.
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ORIGINAL ARTICLE
Prevalence and disability of comorbid social phobia and obsessive–compulsive disorder in patients with panic disorder and generalized anxiety disorder
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Giulia Camuri§, Lucio Oldani§, Bernardo Dell’Osso, Beatrice Benatti, Licia Lietti, Carlotta Palazzo & A. Carlo Altamura
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Department of Neuroscience and Mental Health, University of Milan, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Milano, Italy Abstract Objective. Generalized anxiety disorder (GAD) and panic disorder (PD) are disabling conditions, often comorbid with other anxiety disorders. The present study was aimed to assess prevalence and related disability of comorbid social phobia (SP) and obsessive–compulsive disorder (OCD) in 115 patients with GAD (57) or PD (58). Methods. Patients were classified as having threshold, subthreshold, or no comorbidity, and related prevalence rates, as well as disability (Sheehan Disability Scale, SDS), were compared across diagnostic subgroups. Results. SP and OCD comorbidities were present in 30.4% of the sample, with subthreshold comorbidities present at twice the rate of threshold ones (22.6% vs. 11.3%). Compared with GAD patients, PD patients showed significantly higher subthreshold and threshold comorbidity rates (27.6% and 13.8% vs. 17.5% and 8.8%, respectively). Comorbid PD patients had higher SDS scores than the comorbid and non-comorbid GAD subjects. The presence of threshold SP comorbidity was associated with the highest SDS scores. Conclusions. SP and OCD comorbidities were found to be prevalent and disabling among GAD and PD patients, with higher subthreshold than threshold rates, and a negative impact on quality of life. Present findings stress the importance of a dimensional approach to anxiety disorders, the presence of threshold and subthreshold comorbidity being the rule rather than the exception. Key words: Anxiety disorders, generalized anxiety disorder, panic disorder, subthreshold comorbidity, threshold comorbidity, disability (Received 15 November 2013; accepted 22 August 2014)
Introduction Anxiety disorders are common, comorbid, and disabling conditions, with a lifetime prevalence of approximately 17% in the general population (Baldwin et al. 2010). Among such conditions, generalized anxiety disorder (GAD) and panic disorder (PD) are the most common disorders, with a prevalence of 1.7–3.4% and 1.8%, respectively (Wittchen et al. 2011). In particular, disability related to anxiety disorders is responsible for both economic and human burden, particularly in terms of social and occupational functioning, perceived emotional and physical health, as well as daily life satisfaction (Graystone et al. 2009; Kertz and Woodruff-Borden 2011). Anxiety disorders generally show high rates of psychiatric comorbidities, either as threshold or subthreshold manifestations, and the presence of one disorder seems to increase §
Equally contributing first author. Correspondence: Dott. Bernardo Dell’Osso, Department of Neuroscience and Mental Health, University of Milan, Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Via Francesco Sforza 35, 20122 Milano, Italy. Tel: ⫹ 02-55035994. Fax: ⫹ 02-50320310. E-mail: [email protected]
the probability of having an additional one (Nutt and Ballenger 2003). In fact, the use of a dimensional diagnostic approach, rather than a categorical one, was found to allow a more accurate assessment of subthreshold comorbidity and overall complexity of more severe clinical pictures, in order to establish optimal treatments (Angst et al. 2004, 2009). For instance, a recent study found that individuals with a previous anxiety disorder and current subthreshold anxiety had a greater risk of suffering from subsequent episodes (Kertz and Woodruff-Borden 2011). Therefore, the assessment of subthreshold anxiety represents a crucial step in targeting patients, who might benefit from early interventions and preventive measures (Meulenbeek et al. 2010). Indeed, a recent article by Karsten and colleagues found that the presence of subthreshold anxiety or a prior history of a specific anxiety disorder predicted the disorder recurrence within 2 years, with the highest risk for those who had suffered from both (Karsten et al. 2011). Of note, a recent study reported a 50.6% rate of psychiatric comorbidity in PD, 12.4% of which was represented by subthreshold conditions (Oral et al. 2012). Furthermore, a study focused on subthreshold symptoms in PD found that, after one year of follow-up, threshold comorbidity decreased,
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whereas subthreshold comorbidity increased. In addition, panic symptoms’ severity decreased, whereas subthreshold PD continued to be present and disabling (Karsten et al. 2011). With respect to GAD, current literature shows high levels of psychiatric comorbidity with negative influence on prognosis and quality of life (Angst et al. 2009). In particular, a recent article conducted by Blanco and colleagues found that the prevalence of GAD patients, with at least one psychiatric comorbidity, was up to 90.2%. Comorbidity was represented by mood and anxiety disorders, personality disorders, pathological gambling, and substance abuse (Blanco et al. 2014). Among comorbid anxiety disorders, social phobia (SP) and obsessive–compulsive disorder (OCD) are frequently observed as co-occurring conditions (Wittchen et al. 2000). In particular, different authors have proposed a dimensional approach to SP, conceptualizing the disorder within a continuum of symptom severity, distress, degree of avoidance and impairment, including subthreshold presentation in such classification (Stein et al. 2000; Merikangas et al. 2002). Fehm and colleagues, in turn, identified two other conditions characterized by social anxiety, besides threshold SP, which did not fulfill all criteria of the Dianostic and Statystical Manual of Mental Disorders (DSM): 1) subthreshold presentation, meeting criterion A for DSM, without satisfying the other criterion and 2) symptomatic conditions, characterized by strong social fears, without meeting two or more DSM criteria (Fehm et al. 2008). One of the earliest studies focused on SP spectrum found a link between subclinical presentation and work attendance problems, poor grades in school, conduct disturbances, impaired subjective social support, lack of self-confidence and close friends, use of psychotropic compounds, as well as a greater number of negative life events, chronic medical problems, and mental health visits (Davidson et al. 1994). With respect to OCD, it should be taken into consideration that many subjects with obsessions and/or compulsions might not be diagnosed with OCD (according to DSM criteria), in spite of frequently presenting consequences which are similar to those in patients with threshold OCD, such as reduced quality of life and impaired functioning (De Bruijn et al. 2010). Fineberg and colleagues recently investigated the prevalence and clinical consequences of psychiatric comorbidity in both threshold and subclinical OCD, reporting a high prevalence of mood and anxiety disorders. Authors showed how psychiatric comorbidity rates increased with growing OCD severity (from both subclinical to full syndromes) and negatively impacted patients’ quality of life (Fineberg et al. 2013). More recently, Adam and co-workers found that patients with subthreshold OCD had an increased risk for psychiatric comorbidity, significant daily life impairment, and health care utilization (Adam et al. 2012). The aforementioned studies stress the importance of assessing comorbid subthreshold symptoms as well as threshold conditions in patients with anxiety disorders. Therefore, the aim of the present study was to analyze and compare comorbid (i.e., subthreshold and threshold) SP and OCD, as well as related disability, in a sample of patients primarily suffering from GAD and PD.
Subthreshold comorbidity and disability 249 Methods Study sample included 115 consecutive outpatients, attending the University Department of Psychiatry of the Fondazione IRCCS Ca’ Granda, Ospedale Maggiore Policlinico of Milan, recruited in the period between January 2008 and January 2013, who were cross-sectionally evaluated. Subjects were predominantly citizens living in different city areas, of either gender, aged 18 years and older. To be enrolled in the study, patients were requested to have a primary diagnosis of GAD (n ⫽ 57) or PD (n ⫽ 58), according to DSM-IV-TR criteria (American Psychiatric Association 2000). In fact, patients were excluded when they did not meet GAD or PD criteria as primary diagnoses. No further exclusion criteria were considered; therefore, no patient was excluded from the original sample. After obtaining written informed consent from patients to have their personal records reviewed for research purposes, different socio-demographic and clinical variables (i.e., age at onset, age at first treatment, education level, family history for psychiatric disorders, psychiatric and medical comorbidity, etc.) were collected. In particular, the presence of any comorbid condition (i.e., threshold and subthreshold) was assessed through the SCID-I (First et al. 2002), along with the administration of specific psychometric scales. In particular, in order to evaluate and quantify symptom severity, identify subthreshold anxiety symptoms, and assess disability, the following psychometric scales were administered: Sheehan Disability Scale (SDS) (Sheehan et al. 1996), Liebowitz Social Anxiety Scale (LSAS) (Liebowitz 1987), Yale–Brown Obsessive Compulsive Scale (Y-BOCS) (Goodman et al. 1989a, 1989b), and Panic and Agoraphobia Scale (PAS) (Bandelow 1995). With respect to the PAS, patients were considered to have agoraphobia when they had selected four or more feared/avoided situations in the given list. Due to the lack of uniform consensus on subthreshold SP and OCD definition, they were classified using double criteria: clinical interview and psychometric scales. Therefore, for the purpose of the study, when criteria for full syndromal disorders (i.e., clinical conditions above the diagnostic threshold) were not satisfied at the Structured Clinical Interview for DSM IV Axis I Disorders (SCID-I), in order to qualify as subclinical manifestations, the following cutoff values were established, based on psychometric evaluation (i.e., LSAS and Y-BOCS): subthreshold SP defined as 25 ⱕ LSAS ⱕ 55 and subthreshold OCD defined as 7 ⱕ Y-BOCS ⱕ 15. With respect to subthreshold SP, due to the lack of uniform consensus for the lowest cut-off at the LSAS, we referred to the median value of the sample to set such threshold. With respect to subclinical OCD, according to available literature, a Y-BOCS range between 7 and 15 was identified for such purpose (Federici et al. 2010; Albert et al. 2001). Descriptive and comparative statistical analyses across subgroups (in terms of diagnosis, GAD vs. PD; type of comorbidity, SP vs. OCD) were performed using Student’s t-test for continuous variables and chi-square test for the dichotomous ones (SPSS version 20). Comorbidity rate comparisons were performed considering any comorbidity (threshold ⫹ subthreshold), threshold, and subthreshold separately. The same approach was used for comparing disability levels,
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including non-comorbid cases as well. When evaluating differences across subgroups in terms of pharmacotherapy (mono- vs. poly-therapy), the association of benzodiazepines with other therapies was not considered as an additional treatment. The administered psychometric questionnaires were part of the routine assessment carried out in the out-patients unit of our Department. Since this study had no experimental procedure, set on a purely observational design, no specific Ethical Committee approval was required. Results Main socio-demographic and clinical features of study sample and related subgroups are listed in Table I. The total sample showed a mean age of 45.16 ⫾ 15.43 (GAD, 51.53 ⫾ 15.17 and PD, 38.79 ⫾ 12.95) years, a male/female ratio of approximately 1:2 (total sample 32.2% vs. 67.8%; GAD 31.6% vs. 68.4%; PD 32.8% vs. 67.2%) and a graduation rate of 21.2% (24.6% in GAD vs. 17.9% in PD). A positive family history for psychiatric disorders was observed in 72.6% of the sample, without any significant difference across groups. A mean duration of untreated illness (DUI) of 4 years (47.32 ⫾ 75.19 months) was found for the total sample, with a longer DUI in GAD than that in PD, though not statistically significant (GAD 54.79 ⫾ 80.02 months vs. PD 40.13 ⫾ 70.2 months) (Table I). With respect to age at onset, GAD patients showed a significantly later onset (38.14 ⫾ 14.54 years in GAD vs. 30.40 ⫾ 13.26 years in PD patients; t ⫽ 2.97; p ⫽ 0.004) (Table I). When assessing the age at onset, it was found that patients with any comorbidity (subthreshold or threshold OCD or SP) showed an earlier age at onset than the non-comorbid patients (29.29 ⫾ 12.92 years vs. 36.49 ⫾ 14.51 years; t ⫽ 2.49; p ⫽ 0.014). Such result was not confirmed when considering only subclinical presentations. With respect to pharmacotherapy, the use of poly-therapy, observed in 39.5% of the total sample, was found to be significantly more frequent in GAD versus PD patients (56.1% vs. 22.8%, respectively; χ2 ⫽ 13.25; p ⬍ 0.001). Table I. Main socio-demographic and clinical variables of the study sample. Total sample (n ⫽ 115) Age at onset (years)* DUI (months) Subthreshold SP Subthreshold OCD Any subthreshold Threshold SP Threshold OCD Any threshold Any comorbidity
34.33 ⫾ 14.38
GAD patients (n ⫽ 57) 38.14 14.54*
47.32 ⫾ 75.19 54.79 ⫾ 80.02 16.5% (n ⫽ 19) 15.8% (n ⫽ 9) 7.8% (n ⫽ 9) 3.5% (n ⫽ 2)
PD patients (n ⫽ 58) 30.40 13.26* 40.13 ⫾ 70.20 17.2% (n ⫽ 10) 12.1% (n ⫽ 7)
22.6% (n ⫽ 26) 17.5% (n ⫽ 10) 27.6% (n ⫽ 16) 8.7% (n ⫽ 10) 3.5%§ (n ⫽ 2) 13.8%§ (n ⫽ 8) 4.3% (n ⫽ 5) 7.0% (n ⫽ 4) 1.7% (n ⫽ 1) 11.3% (n ⫽ 13) 8.8% (n ⫽ 5) 13.8% (n ⫽ 8) 30.4% (n ⫽ 35) 21.0%^ (n ⫽ 12) 39.7%^ (n ⫽ 23)
GAD, generalized anxiety disorder; SP, social phobia; OCD, obsessive– compulsive disorder; DUI, duration of untreated illness. *p ⫽ 0.004, t ⫽ 2.97. § p ⫽ 0.05, χ2 ⫽ 3.71. ^ p ⫽ 0.03, χ2 ⫽ 4.69. Bold values are statistically significant.
When considering the presence of any comorbidity (threshold and subthreshold SP and OCD), 30.4% of the total sample was found to have comorbidity, with statistically higher rates in PD than those in GAD (39.7% vs. 21.0%, respectively; χ2 ⫽ 4.69; p ⫽ 0.03) (Table I). Threshold comorbid conditions were less frequent (11.3%) than subclinical ones (22.6%) in the total sample, the first being distributed as follows: 8.7% for SP in the total sample (3.5% in GAD and 13.8% in PD patients) and 4.3% for OCD in the total sample (7% in GAD and 1.7% in PD patients) (Table I). The 16.5% of the total sample met criteria for subthreshold SP, without any significant difference between diagnostic groups (15.8% in GAD and 17.2% in PD patients). In comparison with SP, a lower rate of subthreshold OCD was observed in the whole sample (7.8%), with higher rate for PD in comparison with GAD patients (12.1% vs. 3.5%, respectively). With respect to the presence of “agoraphobia,” 71.7% of PD patients showed such condition, as recorded through the PAAS, considering those fearing/avoiding more than four situations as agoraphobic patients. In particular, 47.4% of the patients with agoraphobia and 33.3% of those without it presented at least one of the aforementioned comorbidities. With respect to comorbidity subtypes, PD patients with agoraphobia showed the following percentages when compared with PD patients without agoraphobia: 18.4% versus 20%, subclinical SP; 13.1% versus 13.3%, subclinical OCD; 18.4% versus 6.6%, threshold SP; and 2.6% versus 6.6%, threshold OCD. The comparison between these subgroups did not show any significant difference from a statistical point of view. In terms of disability, the total score and, more specifically, the three major items of the SDS (family, relationship, and work) were analyzed across different subgroups as follows: non-comorbid versus comorbid GAD and PD patients, subthreshold SP versus threshold SP, and subthreshold OCD versus threshold OCD. Related results are summarized in Table II and graphically presented in Figure 1. PD patients did not show statistically significant differences in comparison with GAD patients, when the overall level of disability was analyzed. However, higher disability levels, in terms of SDS total score and social functioning item, were found in comorbid compared with those in non-comorbid conditions, both in the total sample and in PD patients (total sample: t ⫽ ⫺ 2.10, p ⫽ 0.027 and t ⫽ ⫺ 3.24, p ⫽ 0.002, respectively; PD: t ⫽ ⫺ 2.56, p ⫽ 0.007 and t ⫽ ⫺ 3.07, p ⫽ 0.001, respectively). In terms of SP, significant differences were observed in terms of work disability in the total sample and in GAD patients, full syndromes being more disabling than subclinical ones (total sample: t ⫽ ⫺ 2.75, p ⫽ 0.005; GAD: t ⫽ ⫺ 2.16, p ⫽ 0.001). No significant differences were found when considering OCD comorbidities (Table II). Finally, when evaluating whether patients with any subthreshold condition, regardless of its nature (SP or OCD), had higher disability than non-comorbid patients, they were found to show a higher degree of impairment according to the social item of the SDS (t ⫽ ⫺ 3.04, p ⫽ 0.003). When the same analysis was performed across the diagnostic subgroups, no statistical significance or trend was observed.
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Table II. Disability level (evaluated through the SDS) of the study sample, according to subthreshold and threshold symptoms.
Total sample (n ⫽ 115) Non-comorbid patients (n ⫽ 80) Patients with any comorbidity (n ⫽ 35) Patients with any subthreshold (n ⫽ 26) Patients with any threshold (n ⫽ 13) Total sample with subthreshold SP (n ⫽ 19) Total sample with threshold SP (n ⫽ 10) Total sample with subthreshold OCD (n ⫽ 9) Total sample with threshold OCD (n ⫽ 6) PD patients (n ⫽ 58) PD patients with no comorbidity (n ⫽ 35) PD patients with any comorbidity (n ⫽ 23) PD patients with any subthreshold (n ⫽ 16) PD patients with any threshold (n ⫽ 8) PD patients with subthreshold SP (n ⫽ 10) PD patients with threshold SP (n ⫽ 8) PD patients with subthreshold OCD (n ⫽ 7) PD patients with threshold OCD (n ⫽ 2) GAD patients (n ⫽ 57) GAD patients with no comorbidity (n ⫽ 45) GAD patients with any comorbidity (n ⫽ 12) GAD patients with any subthreshold (n ⫽ 10) GAD patients with any threshold (n ⫽ 5) GAD patients with subthreshold SP (n ⫽ 9) GAD patients with threshold SP (n ⫽ 2) GAD patients with subthreshold OCD (n ⫽ 2) GAD patients with threshold OCD (n ⫽ 4)
Social disability (mean ⫾ SD)
Familiar disability (mean ⫾ SD)
Work disability (mean ⫾ SD)
Disability: total score
6.3 ⫾ 2.9 5.55 3.18* 7.28 2.53* 7.23 ⫾ 2.16 8.75 ⫾ 2.00 6.84 ⫾ 2.29 8.50 ⫾ 2.12 7.78 ⫾ 1.86 7.16 ⫾ 4.49 6.42 ⫾ 3.01 5.25 3.47^ 7.69 1.96^ 7.50 ⫾ 1.78 8.38 ⫾ 2.32 7.00 ⫾ 1.82 8.37 ⫾ 2.32 8.28 ⫾ 1.38 6.50 ⫾ 4.95 6.17 ⫾ 2.82 5.66 ⫾ 3.03 6.05 ⫾ 3.31 6.80 ⫾ 2.70 9.50 ⫾ 1.00 6.66 ⫾ 2.82 9.00 ⫾ 1.41 6 ⫾ 2.82 7.5 ⫾ 5.0
4.87 ⫾ 3.0 4.70 ⫾ 3.24 5.24 ⫾ 2.41 5.35 ⫾ 2.27 5.75 ⫾ 2.89 5.47 ⫾ 2.09 5.10 ⫾ 2.68 5.00 ⫾ 2.91 4.83 ⫾ 4.00 4.77 ⫾ 3.04 4.31 ⫾ 3.48 5.26 ⫾ 2.26 5.12 ⫾ 2.27 5.50 ⫾ 2.20 5.40 ⫾ 1.84 5.50 ⫾ 2.20 5.14 ⫾ 3.02 5.50 ⫾ 3.53 4.96 ⫾ 3.02 4.68 ⫾ 3.19 4.75 ⫾ 3.07 5.70 ⫾ 2.35 6.25 ⫾ 4.34 5.55 ⫾ 2.45 3.50 ⫾ 4.94 4.5 ⫾ 3.53 4.50 ⫾ 5.26
5.53 ⫾ 3.1 5.36 ⫾ 3.19 5.91 ⫾ 2.98 5.35 ⫾ 3.01 7.67 ⫾ 2.29 4.68 3.07§§ 7.70 2.16§§ 6.33 ⫾ 3.00 6.66 ⫾ 4.08 5.62 ⫾ 3.11 4.74 ⫾ 3.66 6.22 ⫾ 2.39 5.69 ⫾ 2.41 7.13 ⫾ 2.03 5.10 ⫾ 2.60 7.12 ⫾ 2.03 6.71 ⫾ 1.70 7.50 ⫾ 3.53 5.44 ⫾ 3.1 5.0 ⫾ 3.23 4.83 ⫾ 4.10 4.80 ⫾ 3.88 8.75 ⫾ 2.50 4.22 3.63°° 10 0.00°° 5 ⫾ 7.07 6.25 ⫾ 4.78
15.92 ⫾ 7.69 14.88 7.93° 18.11 6.65° 17.92 ⫾ 6.0 20.46 ⫾ 7.89 17.00 ⫾ 6.09 21.30 ⫾ 4.99 19.11 ⫾ 6.83 18.67 ⫾ 11.34 16.33 ⫾ 7.46 14.30 8.15§ 19.17 5.08§ 18.31 ⫾ 4.64 21.0 ⫾ 5.45 17.50 ⫾ 4.17 21.0 ⫾ 5.45 20.14 ⫾ 5.14 19.50 ⫾ 12.02 15.51 ⫾ 7.97 15.35 ⫾ 7.81 16.08 ⫾ 8.84 17.30 ⫾ 7.92 19.60 ⫾ 11.54 16.44 ⫾ 7.95 22.50 ⫾ 3.53 15.50 ⫾ 13.43 18.25 ⫾ 12.86
SDS, Sheehan Disability Scale; SD, standard deviation; SP, social phobia; OCD, obsessive–compulsive disorder; PD, panic disorder; GAD, generalized anxiety disorder Bold values are statistically significant..
Discussion Results from the present study suggest that anxiety disorders may frequently show mixed presentation with different symptoms belonging to a common spectrum. In fact, onethird of the total sample showed some degree of comorbidity (threshold or subthreshold). In such perspective, our findings, in relation to general comorbidity, are relevant because almost one-third of the total sample showed some degree of comorbidity, whereas about 70% of patients showed no comorbidity. In addition, the condition of agoraphobia was found to be present in about two-thirds of the patients affected by PD, indicating that the presence of significant agoraphobia (ⱖ 4 items at the PAAS) was associated with the presence of any comorbidity. However, it needs to be stressed that assessed comorbidity was related only to SP and OCD, and it is likely that screening for other anxiety and non-anxiety comorbidities would have given higher rates. With respect to comorbid cases, a higher prevalence of subthreshold disorders, than that of threshold ones, was found for the total sample and subgroups of patients with GAD and PD. In addition, a higher prevalence of subthreshold comorbid conditions was observed in PD than in GAD patients. The presence of subthreshold comorbidity was about twice as frequent in PD as in GAD patients (27.6% vs. 17.5%). In particular, a similar distribution of subthreshold SP was found between the two conditions (17.2% vs. 15.8%), whereas subthreshold OCD was about three
times more frequent in patients affected by PD than GAD (12.1% vs. 3.5%). Such result might be partially explained considering the frequency of hypochondriac symptoms reported by patients with PD. Hypochondriasis, in fact, is a frequent symptom observed in such patients; being a multidimensional syndrome, PD is characterized by the persistent fear of having a serious illness, based on misinterpretation of somatic sensations (Greeven et al. 2006). Similarities between hypochondriasis, obsessive–compulsive and panic symptoms, in terms of phenomenological presentation, have been reported in literature (Abramowitz 2005). The frequent misinterpretation of body sensations, encountered in PD patients, might lead to the development of obsessive beliefs regarding one’s health and ritualistic checking behaviors of one’s general body functions (e.g., checking heart beat subsequent to tachycardia) (Longley et al. 2010). Of note, threshold comorbidities were less frequent than subclinical presentations in the total sample, with higher percentage of OCD in GAD (7.0% vs. 1.7%) and SP in PD patients (13.8% vs. 3.5%). Taken as a whole, such results stress the importance of detecting subthreshold comorbid conditions in anxiety disorders as well as threshold ones, and investigating their onset within the course of illness. A shorter, although not statistically significant, DUI in PD versus GAD patients (on average, 14 months) can be
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25 22,5 21,3
20
19,11 18,67
18,11°
21 19,17
18,25 17,5
17
15
14,88°
20,14 19,5
§
16,44 16,08 15,35 14,3
15,5
Non comorbid patients
§
Patients with any comorbidity Subthreshold SP
10 Threshold SP
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Subthreshold OCD 5 Threshold OCD
0 Total sample
PD
GAD
Figure 1. Graphical explanation of the content of last column in Table II. The total mean Sheehan Disability Scale scores are shown for the comorbidity subgroups (no comorbidities vs. any comorbidities and threshold vs. subthreshold SP/OCD), in the total sample and within the single disorders (PD and GAD). Statistics: °p ⫽ 0.027, t ⫽ ⫺ 2.10, F ⫽ 3.15. §p ⫽ 0.007, t ⫽ ⫺ 2.56, F ⫽ 9.36.
explained considering a generally more acute onset with disabling physical symptoms in PD, leading patients to seek help earlier than GAD subjects, who often show an insidious and more gradual onset (Dell’Osso et al. 2013; Altamura et al. 2010a, 2010b). Another interesting finding is represented by the earlier age of onset in patients with comorbidity (either subthreshold or threshold) versus non-comorbid cases (on average, 7 years earlier). It has already been noticed that early-onset cases of GAD show a higher degree of comorbidity (including social phobia and substance abuse) (Chou 2009), as reported for PD subjects as well (Katerndahl and Talamantes 2000). Such findings remark the need for an early assessment of patients with any comorbid condition belonging to the entire anxiety spectrum, as an earlier age at onset may correlate with a more severe course (e.g., having more comorbidity) and a worse clinical outcome (Gonçalves and Byrne 2012; Le Roux et al. 2005; Goodwin and Hamilton 2002). With respect to disability, it was observed both in the total sample and in PD patients that the presence of any comorbidity negatively influenced the overall individual and social functioning, in particular. This finding might be expected, since SP and OCD, when present either as threshold or subthreshold conditions, can impair both psychosocial and relational skills (Wittchen et al. 2000; Wittchen and Fehm 2001). A similar result was observed for the GAD group, although differences in terms of disability between patients with and without comorbidity were not statistically significant (p ⫽ 0.54 for overall disability; p ⫽ 0.14 for social disability). Indeed, such discordance might indicate a specifically higher disability for PD patients, but should be interpreted cautiously, considering the limited size of the sample.
Another noteworthy finding is represented by the higher social disability, compared with the familial and occupational one, observed for the overall sample and related subgroups (GAD and PD). Apparently, patients with a disorder belon-ging to the anxiety spectrum showed a more severe deficit in social functioning, while occupational and familial areas, in particular, appeared to be less impaired. Such finding might be explained considering that situations eliciting social skills are, often, the first to be avoided by patients affected by anxiety disorders. On the other hand, family represents a protective environment for them, who usually tend to seek domestic shelter and familial reassurance (Rector et al. 2011). Another interesting result was represented by the higher work disability associated with threshold SP versus subclinical SP, both in the total sample and in GAD. From this perspective, there is evidence from literature that SP impairs work and social life more than family life (Wittchen et al., 2000). Several authors, in fact, have shown that individuals affected by this condition tend to be more financially dependent, more frequently underemployed, less productive at work, and underpaid, when compared with non-affected subjects (Wittchen et al., 2000; Schneier et al., 1992; Stein et al., 2000). The varying presence of poly-therapy across diagnostic groups, with a higher rate in GAD versus PD patients (56.1% vs. 22.80%, respectively; p ⬍ 0.001), is worthy of comment. This may be explained by the different clinical presentations of the disorders. GAD, in particular, can determine a polymorphic syndrome with a frequent chronic course, characterized by several symptoms, including sleep disturbance and physical complaints like fatigue, muscle tension, restlessness, and
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DOI: 10.3109/13651501.2014.959972
migraine. Such conditions may require additional treatment, such as low doses of atypical antipsychotics and pregabalin, which represent well-established, non-antidepressant treatments used for the management of GAD patients (Kavan et al. 2009; Zahreddine and Richa 2013; Mellman 2006). On the other hand, PD tends to generate a more acute and definite clinical picture, with frequent but short-lasting somatic complaints, as well as less frequent insomnia, than GAD (Ohayon et al. 1998). However, it should be acknowledged that the use of benzodiazepines was not considered as a poly-therapy, and it may be possible that, in such perspective, PD patients may have shown differences other than those the GAD subjects. Nevertheless, we cannot exclude the possibility that a higher prevalence of poly-therapy, administered for other reasons (e.g., major severity of illness), has somehow influenced prevalence rates of comorbid conditions and related disability. In the context of the reported results, the following limitations should be taken into account. First, present findings are conditioned by the limited sample size, particularly for the assessment of both subthreshold and threshold comorbidities. In this perspective, some non-significant results might be due to type 2 error. Furthermore, the naturalistic way of collecting data entailed the reliability of patients and avai-lable family members: consequently, information may not always be precise. Moreover, the fact that patients with subclinical SP and OCD had higher disability should encou-rage extending the analysis of comorbidity to other anxiety disorders and all affective area, in particular to subclinical depression. From this perspective, a recent article published by Karsten and colleagues showed that the occurrence of anxiety disorders was best predicted by a combination of history of anxiety disorder and subthreshold anxiety, closely followed by a combination of history of depressive disorder and subthreshold depression (Karsten et al. 2011). Finally, as previously pointed out, it should be considered that current pharmacological treatments may have influenced prevalence rates of comorbid conditions as well as related disability, likely underestimating the phenomenon, compared to drug naïve/free patients. In conclusion, present findings indicate a higher prevalence of subthreshold versus threshold OCD and SP comorbidity in patients with GAD and PD, showing significant consequences on patients’ functioning and quality of life and, finally, stressing the importance of assessing subclinical in addition to full syndromal manifestations. Such aspects represent a relevant field of clinical interest and a potential resource for efficiently targeting subjects at risk, who might benefit most from both psychotherapy and early pharmacological intervention strategies. Nevertheless, the inclusion of subclinical presentations into clinical practice assessment needs to be considered with caution, in order to not overpathologize physiological anxiety, such as temperamental shyness and perfectionism, belonging to normal rates of the emotional spectrum. From such perspective, proper and standardized criteria with uniform consensus on specific psychometric scales’ cut-off need to be further investigated.
Key points • • • • •
GAD and PD are potentially disabling disorders, which show high rates of comorbid anxiety both at threshold and subthreshold levels. PD patients show higher subthreshold and threshold comorbidity, particularly in terms of SP. High degree of comorbidity correlates with more severe impairment in the overall quality of life and, particularly, in the social functioning. Within the considered comorbidity spectrum, threshold SP resulted in the most impairing condition. Higher rates of poly-therapy were found in GAD patients when compared with those in PD patients.
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