Available online at www.sciencedirect.com

ScienceDirect Comprehensive Psychiatry xx (2014) xxx – xxx www.elsevier.com/locate/comppsych

Substance use disorders in hospitalized psychiatric patients: The experience of one psychiatric emergency service in Turin Frieri Tiziana a , Montemagni Cristiana a , Crivelli Barbara a , Scalese Mara a , Villari Vincenzo b , Rocca Paola a,⁎ a

b

Psychiatric Section, Department of Neuroscience, University of Turin, Italy Department of Neuroscience and Mental Health, Psychiatric Emergency Service, A.O. Città della Salute e della Scienza di Torino - Presidio Molinette, Turin, Italy

Abstract In the present study we sought: 1) to estimate the frequency of substance use disorders (SUD), and 2) to investigate whether there is a mere association between diagnosis and SUD in a large cohort of patients with severe psychiatric disorders representative of the usual setting and modality of care of a psychiatric emergency service in a geographically well-defined catchment area in Italy, independent of sociodemographic features, anamnestic data and clinical status. The study was conducted between January 2007 and December 2008. The following rating scales were performed: the Clinical Global Impression-Severity (CGI-S), the Global Assessment of Functioning scale (GAF) and the Brief Psychiatric Rating Scale (BPRS). Factors found to be associated (p b 0.05) with SUD[+] in the univariate analyses were subjected to multilevel logistic regression model with a backward stepwise procedure. Among 848 inpatients of our sample 29.1% had a SUD codiagnosis. Eleven factors accounted for 30.6% of the variability in SUD[+]: [a] a Personality Disorder diagnosis, [b] a Depressive Disorder diagnosis, [c] male gender, [d] previous outpatient contacts, [e] single marital status, [f] no previous psychiatric treatments, [g] younger age, [h] lower scores for BPRS Anxiety-depression and [i] BPRS Thought Disturbance, [l] higher scores for BPRS Activation and [m] BPRS Hostile-suspiciousness. The findings are important in identifying (1) the complexity of the clinical presentation of SUD in a inpatients sample, (2) the need for collaboration among health care workers, and (3) the need to develop and apply treatment programs that are targeted at particular risk groups. © 2014 Elsevier Inc. All rights reserved.

1. Introduction The high prevalence of substance use disorders (SUD) in patients with severe mental illness has been well documented in clinical and epidemiologic studies both in Europe [1–3] and in the United States [4–6] with lifetime prevalence that ranges from 29% to 71% and with different comorbid rates in various psychiatric disorders. Several studies have demonstrated a high prevalence of SUD in patients with psychosis or schizophrenia (40–60%), bipolar disorder (11–71%), depression or anxiety (4–80%), personality disorders (PD) (35–91%), and eating disorders (17–46%), depending on whether the sample has originated in the general population or in a clinical setting [7–21]. ⁎ Corresponding author at: Psychiatric Section, Department of Neuroscience, University of Turin, Via Cherasco, 11, 10126 Turin, Italy. E-mail address: [email protected] (R. Paola). http://dx.doi.org/10.1016/j.comppsych.2014.03.018 0010-440X/© 2014 Elsevier Inc. All rights reserved.

The majority of the studies have been limited to community-based samples, the findings of which may not be generalizable to inpatients. Studies on hospital inpatients might be superior to population-based surveys, in that hospital records have rich clinical information that is documented by clinicians and other health professionals. In addition, hospital inpatients often present a clearer spectrum of clinical manifestation from people in the community [22]. Moreover, in these clinical settings, the psychiatric-addictive comorbidity is more common and more severe as compared to outpatient substance use treatment settings [23,24]. Rates of SUD in psychiatric inpatients are thought to range from 12% to 65% and from 48% to 64% for lifetime substance abuse or dependence [25–29]. Although some studies have identified some demographic and clinical variables as predictors of diagnosis of SUD in psychiatric inpatients – as male gender, younger age, single marital status, diagnosis of PD – other authors underlined

2

F. Tiziana et al. / Comprehensive Psychiatry xx (2014) xxx–xxx

that there were no significant differences between patients with and without a SUD [30–34]. However, previous studies have some limitations: the selection of convenience samples, the sample size, the mixture of patients with different treatment histories, the skills and the perspective of the researchers, the choice of diagnostic instruments a lack of consensus regarding the definition of the term “comorbidity”, problems in distinguishing induced and independent disorders, problems in separating psychiatric disorders from the symptoms of intoxication or withdrawal [35–37]. Lastly, earlier studies partially adjusted for potential confounding factors. Thus, in the present study we sought: 1) to estimate the frequency of SUD among inpatients; 2) to investigate whether there is a mere association between diagnosis and SUD in a large cohort of patients with severe psychiatric disorders representative of the usual setting and modality of care of a psychiatric emergency service (PES) in a geographically well-defined catchment area in Italy, independent of sociodemographic features, anamnestic data and aspects of clinical presentation. Italian psychiatric services are public, based on catchment areas and are available to everyone. Almost all patients with psychiatric disorders or SUD are primarily referred to the psychiatric department of the local hospital for their catchment area. This allowed us to study a sample of all patients consecutively admitted within a specified time period from one catchment area.

2. Methods 2.1. Subjects The present study was conducted in the period between January 2007 and December 2008 in the PES, Department of Neuroscience and Mental Health, A.O. Città della Salute e della Scienza di Torino – Presidio Molinette, Turin. It is part of the first hospital in Italy concerning the size and the indices for complexity of care. Due to the local organization of mental health that has divided the urban area of the city into zones, this PES is the only acute inpatient psychiatric facility of reference for the population of the corresponding zone. It provides emergency care for a population of approximately 120.000 inhabitants with a total of almost 450 admissions every year. Patients admitted in the ward were identified by our researcher team (T.F., C.M.) and approached within 72 h of admission, through ongoing contacts with PES clinical staff. The interviewing psychiatrists were never members of the patients' treating team and were not involved in the clinical activity of the emergency department during the study period. All consecutive patients in the 18–65 years age group were asked to participate if: 1) they had sufficient comprehension skills to understand clinicians' questions and verbal information in order to avoid possible distorsion in responding to assessment questions; 2) they were able to

read and speak the Italian language; 3) they provided verbal assent to participate in the study. The information on drug abuse was obtained in a nonthreatening and supportive atmosphere in order to encourage forthright responses from the patients, and the issue of confidentiality was stressed. Diagnosis of SUD was determined according to the DSMIV-TR [38]. All patients underwent clinical examination. Diagnoses, formulated by the treating consultant psychiatrist, were confirmed using the Structured Clinical Interview for DSM-IV disorders (SCID-I and SCID-II) [39,40]. All available psychiatric diagnoses were examined and classified according to the following four main categories: Non Affective Psychoses, Depressive Disorders (DD), Mania, PD. Subjects with a current disorder other than those abovementioned were excluded. To avoid duplication, only data for the first hospitalization of patients who had multiple hospitalizations were included in this analysis, thus reducing the potential adverse effect of clustering or nonindependence of hospitalizations within patients. The protocol was approved by a local research ethics committee (LREC) (CEI 185). Because data collection was integrated as part of the regular diagnostic assessment procedure and of the quality check processes that don't influence therapeutic decisions or outcomes and because the data were analysed anonymously, the LREC agreed that informed consent was not required. All personally sensitive information contained in the database used for this study was previously de-identified according to the Italian legislation. The study was carried out in accordance with the Declaration of Helsinki (with amendments) and Good Clinical Practice. 2.2. Assessment instruments Upon patients' arrival at the PES a semistructured interview was filled out. The data were extracted from medical and nursing records and medication schedules of patients who were admitted in the PES during the study period. Further, missing data were collected from the patient after the remission of the acute episode or obtained by archival sources as well as detailed reports from community mental health teams and primary care physicians. Clinical ratings included the Clinical Global Impression – Severity (CGI-S) [41], the Global Assessment of Functioning scale (GAF) [42], and the Brief Psychiatric Rating Scale (BPRS) [43]. The five domains scores calculated were as follows: Anxiety-Depression, Anergia, Thought disturbance, Activation and Hostile-suspiciousness. All assessments were performed by the same well-trained experienced interviewing psychiatrists (T.F., C.M.) who were blinded to the diagnosis, psychiatric history, and pharmacological treatment. In an attempt to reduce inter-rater variability, raters were trained to administer the psychometric tools according to common standards. Efforts were made to maintain inter-rater reliability across the entire study period,

F. Tiziana et al. / Comprehensive Psychiatry xx (2014) xxx–xxx

including careful calibration and standardization procedures and regular, in-depth review of a sample of interviews with the lead author. 2.3. Statistical analyses Given the normal distribution of data, preliminary comparisons of the socio-demographic, clinical and psychopathological characteristics of inpatients with versus without a DSM-IV-TR SUD diagnosis were performed using univariate analyses (ANOVA) for continuous variables and contingency tables (Chi-square test) for categorical variables. Factors found to be associated with a SUD in these preliminary analyses at p b 0.05 level were then subjected to multilevel logistic regression model with a backward stepwise procedure to determine odd ratios (ORs) and their 95% confidence intervals (C.I.). It was constructed a model with diagnosis of a comorbid SUD as the dependent variable and with the following steps: first, assessing the association with diagnoses, without controlling for confounding factors (step 1); second, entering diagnoses and socio-demographic factors (gender, age, marital status, education, employment) (step 2); third, entering diagnoses, socio-demographic factors and data concerning psychiatric history (length of illness, previous admissions, previous compulsory admissions (CAs) within previous 5 years, previous outpatient contact in the past 6 months, previous psychiatric treatment in the last 2 weeks, previous suicidal attempts) (step 3); fourth, entering diagnoses, socio-demographic factors, data concerning psychiatric history and aspects of clinical presentation (BPRS, CGI-S and GAF scores and CA) (step 4). All odd ratios (OR) are presented with 95% C.I. and p b 0.05. For all models, R 2 Nagelkerke was calculated to determine the percentage of variability explained. R 2 ranges from 0 (random predictions) to 1.0 (perfect predictions). Statistical analyses were performed using the software system SPSS, version 17 (SPSS Inc., 2008). 3. Results During the 24-months period of inclusion, 951 acute patients were admitted in the PES of the Città della Salute e della Scienza di Torino – Presidio Molinette, of those 894 were eligible for the study because they fulfilled the above mentioned criteria. The final sample consisted of 848 inpatients, because of 24 patients were discharged before the assessment and 22 had missing data. The general socio-demographic characteristics of the whole sample has been recently reported [44,45]. As the primary basis for comparison, the whole sample was divided into two sub-groups based on the presence/ absence of a SUD in the previous 6 months: 247 (29.1%) inpatients with a DSM-IV-TR SUD diagnosis (SUD[+]) versus 601 inpatients without a SUD (SUD[−]). Among PD with SUD[+] (88/158) we found numerically more patients in Cluster B (53.41%) than Cluster C (35.23%) or Cluster A

3

(11.36%). Among the SUD[+] patients, 26% abused illicit drugs (sedatives, stimulants, analgesics, benzodiazepines), 36% abused alcohol, and 38% were polysubstance abusers. Initial univariate comparison of patients with versus without a SUD found 15 factors that differed significantly (Table 1). SUD[+] were more often men, single and averaged 8.37 years younger than those without. SUD was somewhat more prevalent among patients diagnosed with PD. There were differences in most anamnestic factors, including lesser length of illness, more previous compulsory admissions, more previous outpatient contacts and less previous psychiatric treatments. SUD[+] patients at hospital admission showed less anxiety-depression, anergia, and thought disturbance, and more activation and hostile-suspiciousness than those without SUD. Multilevel logistic regression model found that eleven of these factors remained significantly and independently associated with SUD[+] (Table 2). They were, in rankorder: [a] a PD diagnosis, [b] a DD diagnosis, [c] male gender, [d] previous outpatient contacts, [e] single marital status, [f] no previous psychiatric treatments, [g] younger age, [h] lower scores for BPRS Anxiety-depression and [i] BPRS Thought Disturbance, [l] higher scores for BPRS Activation and [m] BPRS Hostile-suspiciousness. For model 1, Nagelkerke R 2 was 0.105 (10.5% “variability” explained), indicating poor prediction; model 2 accounted for the 22.7% of the variability; for model 3 Nagelkerke R 2 was 0.254 (25.4% “variability” explained), while overall, the percentage of correctly predicted cases in model 4 was 30.6% (Nagelkerker R 2 = 0.306), indicating good prediction.

4. Discussion This is one of the largest comparisons of Italian patients with severe psychiatric disorders, with and without comorbid SUD referring to a PES in a geographically welldefined catchment area in Italy. As characteristics of inpatients last but not least depend on the countries' legislation and local practice, we mainly focused our comparison on Italian studies, whenever possible. As for the first aim, in our study the overall comorbidity with any SUD in the past 6 months was found to be 29.1%. In the PERSEO (psychiatric emergency study and epidemiology) survey, a naturalistic, observational clinical survey in 62 PESs distributed throughout Italy, 18.7% inpatients were alcohol abusers, 3.5% were drug abusers, and 4.9% of them received a substance abuse, dependence diagnosis at the admission [46–48]. Prevalence rates of SUD among our inpatients were found to be as high as those recently found in the very few studies of substance abuse in hospitalized patients conducted in Italy, in either psychiatric or general hospitals [49–55], whose reported rates of psychiatric inpatients' SUD (ranging from 0.5% to 48%) appeared to be lower than in other western countries. The reasons are

4

F. Tiziana et al. / Comprehensive Psychiatry xx (2014) xxx–xxx

Table 1 Socio-demographic and clinical characteristics as a function of current DSM-IV-TR SUD diagnosis.

N (%) Male, n (%) Age, years, mean ± SD Single marital status, n (%) Education, years, mean ± SD Unemployed, n (%) Length of illness, years, mean ± SD Diagnostic groups, n (%) Non affective psychoses Depressive disorders Mania Personality disorders Compulsory admission, n (%) Self-injurious behavior, n (%) Length of stay (LOS), days, mean ± SD Previous admissions, n (%) Previous CAs, n (%) Previous suicidal attempts, n (%) Previous outpatient contacts, n (%) Previous psychiatric treatments, n (%) BPRS, Total score, mean ± SD BPRS, Anxiety-depression, mean ± SD BPRS, Anergia, mean ± SD BPRS, Thought disturbance, mean ± SD BPRS, Activation, mean ± SD BPRS, Hostile-suspiciousness, mean ± SD CGI-S, mean ± SD GAF, Total score, mean ± SD

SUD [+]

SUD [−]

F/χ 2a

P

247 (29) 154 (62) 37.69 ± 10.84 204 (83) 9.56 ± 3.20 68 (28) 7.29 ± 5.97

601 (71) 252 (42) 45.32 ± 14.78 407 (68) 9.55 ± 3.41 180 (30) 9.68 ± 8.81

— 29.254 53.910 19.224 0.004 0.423 15.324 69.268

— 0.000 0.000 0.000 0.949 0.287 0.000 0.000

88 (36) 50 (20) 21 (8) 88 (36) 53 (21) 28 (11) 9.34 ± 5.31 187 (76) 65 (26) 41 (17) 204 (83) 189 (77) 46.66 ± 12.67 11.43 ± 3.06 9.13 ± 3.39 8.62 ± 4.95 9.51 ± 4.34 8.09 ± 4.27 4.89 ± 0.99 45.27 ± 9.63

265 (44) 163 (27) 103 (17) 70 (12) 93 (15) 59 (10) 10.95 ± 5.78 429 (71) 123 (20) 117 (19) 463 (77) 501 (83) 47.81 ± 12.80 12.77 ± 3.91 10.21 ± 3.74 9.54 ± 5.09 8.27 ± 4.29 7.18 ± 4.17 5.03 ± 1.03 44.82 ± 10.46

4.397 0.439 14.165 1.650 3.472 0.950 3.215 5.407 1.422 23.484 15.505 5.874 14.611 8.157 3.333 3.332

0.024 0.292 0.000 0.115 0.039 0.191 0.043 0.014 0.233 0.000 0.000 0.016 0.000 0.004 0.068 0.565

Abbreviations: SUD = Substance Use Disorder. a Chi-square tests: gender, marital status, unemployment, CA, previous CAs, previous suicidal attempts, previous outpatient contact, previous treatment, self-inflicted injuries. One-way ANOVA: age, education, length of illness, length of stay.

unknown. One possible explanation is the low admission rate of patients with a diagnosis of SUD to Italian PESs. Actually, Italian Mental Health Departments are not involved in the treatment of patients with a primary diagnosis of SUD [56]. Alcohol was found to be the most commonly abused substance in the SUD[+] group. The high prevalence of alcohol abuse/dependence in our sample is similar to other research on adult populations [6,57,58]. This finding is highly expected since alcohol remains the most available and easily accessible substance [34], as Italy is an example of traditionally wet cultures, where drinking typically is frequent and regularly integrated into daily life and activities (e.g., is consumed with meals). Moreover, in our sample there was also a high proportion (38%) of polysubstance abusers. These data are consistent with previous studies that found a prevalence until 50% [34,59–62]. As for the second aim, this study examined comorbidity with the most common mental health disorders and explored the associations with these mental disorders individually. It is noted that, after controlling for socio-demographic characteristics, psychiatric history, and clinical status, SUD was significantly associated with PD (OR = 5.324), and DD (OR = 2.842).

SUD among inpatients presenting a PD (55.7%) was within the range of the reported rates in clinical samples (35–91%) [63–67]. The prevalence of PD in SUD[+] patients (36%) is far above that found in epidemiological studies of PD [68–70]. The selection bias of hospital wards results in a higher prevalence of comorbidity in clinical samples. This is often referred to as Berkson's fallacy [71]. After controlling for socio-demographic characteristics, psychiatric history, and clinical status, PD raised the SUD risk significantly more than fivefold as compared to Mania, highlighting a strong association between PD and SUD, in line with most other studies [72–74]. While it is not ascertainable from these cross-sectional data, there are several ways to interpret these finding. First, SUD can be regarded as due, in part, to deficits in affect regulation and impulse control, which are considered characteristic of persons with Cluster B PD, mainly borderline PD [75]. Second, it has been shown a strong association between SUD and sensation-seeking and novelty-seeking traits [51,76–79], that might interact with psychiatric symptoms and favour the onset of SUD [80–86]. Lastly, substance misuse could in part represent, in patients with co-occurrence of SUD and other psychiatric disorders, an attempt to alleviate specific

Ref. 1.373 (0.765–2.464) 2.842 (1.434–5.634)⁎ 5.324 (2.766–10.247)⁎⁎⁎ 2.710 (1.887–3.893)⁎⁎⁎ 0.970 (0.956–0.985)⁎⁎⁎ 1.569 (1.013–2.432)⁎ 0.974 (0.946–1.003) 1.500 (0.952–2.365) 1.960 (1.132–3.393)⁎ 1.202 (1.270–3.816)⁎⁎ 0.906 (0.858–0.956)⁎⁎⁎ 0.916 (0.873–0.968)⁎⁎ 1.048 (1.001–1.097)⁎ 1.095 (1.035–1.157)⁎⁎ (0.682–2.106) (1.035–3.529)⁎ (3.112–10.619)⁎⁎⁎ (1.884–3.790)⁎⁎⁎ (0.954–0.983)⁎⁎⁎ (0.950–2.244) (0.948–1.004) (1.049–2.439)⁎ (1.250–3.719)⁎⁎ (1.448–4.318)⁎⁎⁎ Ref. 1.198 1.911 5.749 2.672 0.968 1.460 0.976 1.599 2.156 2.500 Ref. 1.259 (0.720–2.201) 1.844 (1.012–3.360)⁎ 5.863 (3.202–10.736)⁎⁎⁎ 2.877 (2.040–4.058)⁎⁎⁎ 0.965 (0.952–0.978)⁎⁎⁎ 1.518 (1.004–2.295)⁎

Clinical status

Psychiatric history

Socio-demographic characteristics

Abbreviations: SUDs = Substance Use Disorders. ⁎⁎⁎ p ≤ 0.001. ⁎⁎ p ≤ 0.01. ⁎ p ≤ 0.05.

Ref. 1.629 (0.961–2.761) 1.505 (0.854–2.650) 6.166 (3.506–10.844)⁎⁎⁎ Mania (Ref.) Non affective psychoses Depressive disorders Personality disorders Male Younger age Single marital status Shorter length of illness Previous CAs Previous outpatient contacts No previous psychiatric treatments BPRS, Anxiety-depression BPRS, Thought disturbance BPRS, Activation BPRS, Hostile-suspiciousness Diagnoses

Table 2 Factors associated with SUD [+] patients.

Step 1 OR (C.I. 95%)

Step 2 OR (C.I. 95%)

Step 3 OR (C.I. 95%)

Step 4 OR (C.I. 95%)

F. Tiziana et al. / Comprehensive Psychiatry xx (2014) xxx–xxx

5

symptoms or at least painful affects and subjective states of distress as well as to alleviate boredom and to socialize [87–92], in line with the self-medication hypothesis [93–95]. Inpatients presenting with a DD had significantly lower prevalence rate of SUD[+] as compared to inpatients with Non Affective Disorders and PD, and they had significantly higher prevalence rate of SUD[+] as compared to inpatients with Mania. In particular, these data were within the broad range of the reported rates for major depressive disorder both in international studies (9–50%) [96–98] and in Italian studies conducted in PESs (3.3–43.5%) [50,51,54]. Moreover, we found a one and half-fold increased SUD risk for patients with DD compared with patients with Mania, without controlling for confounding factors; however, this finding was not statistically significant. This link persisted, raised, and became statistically significant only when analyses controlled for socio-demographic characteristics, for psychiatric history, and for clinical status. This could be due to the fact that in our sample patients with DD were significantly older and more likely to be married as compared to patients with other diagnoses. Patients with DD were also more likely to be female as compared to patients with non affective psychosis and mania. There are some possible explanations for the factors and processes that may give rise to the relationship between DD and SUD. Some SUD and mood disorders may share a common, but still undefined, biological basis [99–102], including dopaminergic arousal and reward systems [103–105]. However, a lack of reliable information about the duration of the SUD before hospitalization and of their timing with respect to the index illness makes it impossible to exclude use of substances to mitigate symptoms or self-medicate an episode of illness [54]. Consistent with previous reports, SUD was associated with male sex [11,106–111], younger age [55,107,111– 114], and single marital status [106]. Of note, no significant differences were found between SUD[+] and SUD[−] as regards working and social functioning, a finding consistent with the CATIE study results where, compared with abstinence, substance use and SUD, unless they involved cocaine use, were associated with higher or equal overall psychosocial functioning [11,115]. Particularly, male gender raised the SUD risk almost threefold in our study, after controlling for psychiatric history and clinical status. The sex difference may be due to higher rates of exposure to heavy alcohol- and drug-use in males than in females and this is particularly true in males with mental disorders [116,117] and in psychiatric inpatients [108,118–121]. However, in the last decades, gender roles have changed in many societies and some studies suggest that the drinking and substance use patterns of men and women are converging [122]. However, in countries where gender equality has remained static, this trend has not been observed [122–124]. In Italy, many societal factors have changed towards more gender equality. However, in most countries of the world, such as Italy, substance misuse in women is often more stigmatised and carries extreme

6

F. Tiziana et al. / Comprehensive Psychiatry xx (2014) xxx–xxx

condemnation from society. Women's access to treatment is hindered by cultural taboos and clashes with childcare responsibilities [125,126]. Thus, it is likely that substance abuse among women is grossly under-reported and under-treated. As for the relationship between the single marital status and SUD it has been reported that the comorbidity with SUD is associated with a several negative effects on the family, including greater burden of care [127,128] and family conflict, further straining family relationships [128–131]. The result of the high stress of coping with a relative with a co-occurring disorder is often the loss of family support and ensuing negative outcomes such as housing instability and homeless [132,133]. As regards psychiatric history, our results have shown an almost twofold SUD risk in inpatients with previous outpatient contact in the past 6 months. The particularly higher proportion of previous outpatients contact in the past 6 months in SUD[+] patients could be viewed as a sort of help-seeking or seeking treatment behavior. However, compared to SUD[−] patients, SUD[+] inpatients were less likely to have any psychiatric treatment in the previous 2 weeks. Earlier studies have found both significantly greater rates of help-seeking behavior among SUD comorbid patients, mainly the symptomatic ones [134–137] both failure to engage in the proposed treatment, reflecting a poor adherence with the therapeutic project in these patients [59]. Lastly, there were only minor differences in most psychopathological symptoms, with SUD[+] patients at hospital admission showing lower anxiety depression and thought disturbance and more activation and hostilitysuspiciousness, as previously reported [31,138,139]. Our study had several limitations. First, our study was carried out at a single facility, thus specific hospital practices and regional characteristics may have influenced the results. Moreover, the majority of the studies on this issue were mainly performed in inpatient psychiatric dual diagnosis unit of public city hospitals. However, this study showed similar comorbidity rates to other studies. This might indicate that there is some validity in what this study has found. Secondly, the SCID II was administered to patients in an acute, inpatient setting. Many patients entered the unit with active Axis I symptoms. Although an effort was made to interview patients when they were assessed to be clinically stable, it is possible that residual state effects of either their recent substance abuse or recent active psychiatric symptoms could have affected the validity of the SCID II [59]. Third, this study does not give a detailed account of a particular psychiatric disorder in relation to use of a particular drug. Fourth, our cross-sectional data cannot address issues pertaining to the longitudinal associations of the disorders. Fifth, in our study, the data concerning the temporal correlation between appearance of substance abuse and mental problems were obtained mainly from self-report and medical files. An obvious limitation is rooted in the difficulties of obtaining objective retrospective information [32].

Despite these limitations, there are some points of strength of this study. First, data were representative of the clinical activity over a 24-month period in the PES in a geographically well-defined catchment area in the center of one of the biggest cities in Italy. Second, the catchment area based concept makes it possible to study a complete naturalistic sample, while most of the earlier studies have chosen convenience samples. Third, data were gathered by only one PES reducing the variability in multicenter studies in terms of different treatment strategies of each facility. Fourth, our sample is high in number and in distribution of diagnoses. Fifth, diagnoses were based on structured clinical interviews and not based on treating clinicians' judgments nor retrieved from chart reviews as in many research on psychiatric emergency. In conclusion, this study aims to extend our knowledge of comorbidity between psychiatric disorders and SUD among psychiatric inpatients. The findings are important in identifying the complexity of the clinical presentation of SUD in an inpatients sample [140]. Indeed, clinicians should address sociodemographic features, anamnestic data and clinical status to optimize treatment response, to increase medication adherence and to manage problematic pharmacokinetic. Moreover, they should investigate how comorbidity affects interventions for either SUD or psychiatric diagnoses, in particular in patients with DD and PD. Our findings are also important in identifying the need for collaboration among health care workers because these patients require intensive mental and substance abuse care, ideally simultaneously and in a coordinated manner, in particular if they had no psychiatric treatments before the hospitalization. In fact, these risk groups need to develop and apply treatment programs in order to achieve effective resource utilization, identifying cross-disciplinary casemanagement and alleviating logistical hurdles, to greatly improve individual outcome and to provide the quality of inpatients treatment setting. References [1] Verdoux H, Tournier M. Cannabis use and risk of psychosis: an etiological link? Epidemiol Psichiatr Soc 2004;13:113-9. [2] Fioritti A, Ferri S, Galassi L, Warner R. Substance use among the mentally ill: a comparison of Italian and American samples. Community Ment Health J 1997;33:429-42. [3] Wittchen HU, Perkonigg A, Reed V. Comorbidity of mental disorder and substance use disorder. Eur Addict Res 1996;2:36-47. [4] Addington J, Addington D. Patterns, predictors and impact of substance use in early psychosis: a longitudinal study. Acta Psychiatr Scand 2007;115:304-9. [5] Kessler RC. The epidemiology of dual diagnosis. Biol Psychiatry 2004;56:730-7. [6] Regier DA, Farmer MD, Rae DS, Locke BZ, Keith SJ, Judd LL, et al. Comorbidity of mental disorders with alcohol and other drug abuse: results from the Epidemiologic Catchment Area (ECA) Study. JAMA 1990;264:2511-8. [7] Harrop EN, Marlatt GA. The comorbidity of substance use disorders and eating disorders in women: prevalence, etiology, and treatment. Addict Behav 2010;35:392-8.

F. Tiziana et al. / Comprehensive Psychiatry xx (2014) xxx–xxx [8] Zikos E, Gill KJ, Charney DA. Personality disorders among alcoholic outpatients: prevalence and course in treatment. Can J Psychiatry 2010;55:65-73. [9] Preuss UW, Johann M, Fehr C, Koller G, Wodarz N, Hesselbrock V, et al. Personality disorders in alcohol-dependent individuals: relationship with alcohol dependence severity. Eur Addict Res 2009;15:188-95. [10] Echeburua E, De Medina RB, Aizpiri J. Comorbidity of alcohol dependence and personality disorders: a comparative study. Alcohol Alcohol 2007;42:618-22. [11] Swartz MS, Wagner HR, Swanson JW, Stroup TS, McEvoy JP, Canive JM, et al. Substance use in persons with schizophrenia: baseline prevalence and correlates from the NIMH CATIE study. J Nerv Ment Dis 2006;194:164-72. [12] Sorvaniemi M, Hintikka J. Recorded psychiatric comorbidity with bipolar disorder – a Finnish hospital discharge register study. Nord J Psychiatry 2005;59:531-3. [13] Krueger RF. Psychometric perspectives on comorbidity. In: Helzer JEE, & Hudziak JJE, editors. Defining Psychopathology in the 21st Century: DSM-V and beyond. Washington, DC: American Psychiatric Publishing; 2002. p. 41-54. [14] Blanchard JJ, Brown SA, Horan WP, Sherwood AR. Substance use disorders in schizophrenia: review, integration, and a proposed model. Clin Psychol Rev 2000;20:207-34. [15] Angold A, Costello E, Erkanli A. Comorbidity. J Child Psychol Psychiatry 1999;40:57-87. [16] Lynskey MT. The comorbidity of alcohol dependence and affective disorders: treatment implications. Drug Alcohol Depend 1998;52:201-9. [17] Rounsaville BJ, Kranzler HR, Ball S, Tennen H, Poling J, Triffleman E. Personality disorders in substance abusers: relation to substance use. J Nerv Ment Dis 1998;186:87-95. [18] Van Horn DH, Frank AF. Substance-use situations and abstinence predictions in substance abusers with and without personality disorders. Am J Drug Alcohol Abuse 1998;24:395-404. [19] Kranzler HR, Satel S, Apter A. Personality disorders and associated features in cocaine-dependent inpatients. Compr Psychiatry 1994;35:335-40. [20] DeJong CA, van den Brink W, Harteveld FM, van der Wielen EG. Personality disorders in alcoholics and drug addicts. Compr Psychiatry 1993;34:87-94. [21] Sabshin M. Comorbidity: a central concern of psychiatry in the 1990's. Hosp Commun Psychiatry 1991;42:345. [22] Xiong Lai HM, Huang QR. Comorbidity of mental disorders and alcohol- and drug-use disorders: Analysis of New South Wales inpatient data. Drug Alcohol Rev 2009;28:235-42. [23] Duffy SQ, Zarkin GA, Dunlop LJ. Do client characteristics affect admission to inpatient versus outpatient alcohol treatment in publicly monitored programs? In: & Council CL, editor. Health Services Utilization by Individuals with Substance Abuse and Mental Disorders (Chapter 4). Rockville, MD: DHHS SAMHSA Office of Applied Studies; 2008. [24] Mattson ME. The search for a rational basis for treatment selection. In: & Galanter M, editor. Recent Developments in Alcoholism, 1. New York: Kluwer Academic/Plenum Publishers; 2003. p. 97-113. [25] Cantwell R, Brewin J, Glazebrook C, Dalkin T, Fox R, Medley I, et al. Prevalence of substance misuse in first-episode psychosis. Br J Psychiatry 1999;174:150-3. [26] Havassy BE, Arns PG. Relationship of cocaine and other substance dependence to well-being of high-risk psychiatric patients. Psychiatr Serv 1998;49:935-40. [27] Lehman AF, Myers CP, Corty E, Thompson JW. Prevalence and patterns of “dual diagnosis” among psychiatric inpatients. Compr Psychiatry 1994;35:106-11. [28] Brady K, Casto S, Lydiard RB, Malcolm R, Arana G. Substance abuse in an inpatient psychiatric sample. Am J Drug Alcohol Abuse 1991;17:389-97.

7

[29] Dixon L, Haas G, Weiden PJ, Sweeney J, Frances AJ. Drug abuse in schizophrenic patients: clinical correlates and reasons for use. Am J Psychiatry 1991;148:224-30. [30] Steingrímsson S, Carlsen HK, Sigfússon S, Magnússon A. The changing gender gap in substance use disorder: a total populationbased study of psychiatric in-patients. Addiction 2012;107:1957-62. [31] Vincenti A, Ventriglio A, Baldessarini RJ, Talamo A, Fitzmaurice G, Centorrino F. Characteristics and Clinical Changes during Hospitalization in Bipolar and Psychotic Disorder Patients with versus without Substance-Use Disorders. Pharmacopsychiatry 2010;43:225-32. [32] Katz G, Durst R, Shufman E, Bar-Hamburger R, Grunhaus L. Substance Abuse in Hospitalized Psychiatric Patients. IMAJ 2008;10:672-5. [33] Møller T, Linaker OM. Symptoms and lifetime treatment experiences in psychotic patients with and without substance abuse. Nord J Psychiatry 2004;58:237-42. [34] Karam EG, Yabroudi PF, Melhem NM. Comorbidity of Substance Abuse and Other Psychiatric Disorders in Acute General Psychiatric Admissions: A Study From Lebanon. Compr Psychiatry 2002;43:463-8. [35] Langås AM, Malt UF, Opjordsmoen S. Comorbid mental disorders in substance users from a single catchment area – a clinical study. BMC Psychiatry 2011;11:25. [36] Goldsmith RJ. Overview of psychiatric comorbidity. Practical and theoretic consideration. Psychiatr Clin North Am 1999;22:331-49. [37] Miller NS, Fine J. Current epidemiology of comorbidity of psychiatric and addictive disorders. Psychiatr Clin North Am 1993;16:1-10. [38] Psychiatric Association American. Diagnostic and Statistical Manual of Mental Disorders. . [text revised]. 4th ed. Washington, DC: American Psychiatric Association; 2000. [39] First MB, Gibbon M, Spitzer RL, et al. Structured Clinical Interview for DSM-IV Disorders (SCID). Washington, DC: American Psychiatric Press; 1997. [40] First MB, Spitzer RL, Gibbon M, et al. User's guide for the Structured Clinical Interview for DSM-IV Axis II Personality Disorders: SCIDII. Washington, DC: American Psychiatric Press; 1997. [41] Guy W. ECDEU Assessment Manual for Psychopharmacology. . Revised. DHEW Publication No. (ADM) 76-338; 1976. [42] Jones SH, Thormicroft G, et al. A brief mental health outcome scale. Reliability and validity of the Global Assessment of Functioning (GAF). Br J Psychiatry 1995;166:654. [43] Overall JE, Gorham DR. The Brief Psychiatric Rating Scale. Psychol Rep 1962;10:799. [44] Frieri T, Montemagni C, Rocca G, Rocca P, Villari V. Clinical outcome and length of stay in an Italian Psychiatric Emergency Service. Soc Psychiatry Psychiatr Epidemiol 2013;48:1013-20. [45] Montemagni C, Frieri T, Villari V, Rocca P. Compulsory admissions of emergency psychiatric inpatients in Turin: the role of diagnosis. Prog Neuropsychopharmacol Biol Psychiatry 2012;39:288-94. [46] Ballerini A, Boccalon R, Boncompagni G, Casacchia M, Margari F, Minervini L, et al. An observational study in psychiatric acute patients admitted to General Hospital Psychiatric Wards in Italy. Ann Gen Psychiatry 2007;6:2. [47] Ballerini A, Boccalon R, Boncompagni G, Casacchia M, Margari F, Minervini L, et al. Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology) survey. Ann Gen Psychiatry 2007;6:29. [48] Preti A, Rucci P, Gigantesco A, Santone G, Picardi A, Miglio R, et al, The PROGRES-Acute Group. Patterns of care in patients discharged from acute psychiatric inpatient facilities. A national survey in Italy. Soc Psychiatry Psychiatr Epidemiol 2009;44:767-76. [49] Mauri MC, Rovera C, Paletta S, De Gaspari IF, Maffini M, Altamura AC. Aggression and psychopharmacological treatments in major psychosis and personality disorders during hospitalisation. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:1631-5.

8

F. Tiziana et al. / Comprehensive Psychiatry xx (2014) xxx–xxx

[50] Tondo L, Lepri B, Cruz N, Baldessarini RJ. Age at onset in 3014 Sardinian bipolar and major depressive disorder patients. Acta Psychiatr Scand 2010;121:446-52. [51] Bizzarri JV, Rucci P, Sbrana A, Miniati M, Raimondi F, Ravani L, et al. Substance use in severe mental illness: self-medication and vulnerability factors. Psychiatry Res 2009;165:88-95. [52] Colasanti A, Natoli A, Moliterno D, Rossattini M, De Gaspari IF, Mauri MC. Psychiatric diagnosis and aggression before acute hospitalisation. Eur Psychiatry 2008;23:441-8. [53] Gaddini A, Franco F, Biscaglia L, Di Lallo D. An urban Italian study on emergency room utilisation by immigrants suffering from mental disorders in Rome, 2000–2004. Eur Psychiatry 2008;23:118-24. [54] Minnai GP, Tondo L, Salis P, Ghiani C, Manfredi A, Paluello MM, et al. (the International Consortium for Bipolar Disorders Research). Secular trends in first hospitalizations for major mood disorders with comorbid substance use. Int J Neuropsychopharmacol 2006;9:319-26. [55] Maremmani I, Lazzeri A, Pacini M, Lovrecic M, Placidi GF, Perugi G. Diagnostic and symptomatological features in chronic psychotic patients according to cannabis use status. J Psychoactive Drugs 2004;36:235-41. [56] Raja M, Azzoni A. Comparison of three antipsychotic in the emergency psychiatric setting. Hum Psychopharmacol Clin Exp 2003;18:447-52. [57] Bucholz KK. Nosology and epidemiology of addictive disorders and their comorbidity. Psychiatr Clin North Am 1999;22:221-40. [58] Hien D, Zimberg S, Weisman S, First M, Ackerman S. Dual diagnosis subtypes in urban substance abuse and mental health clinics. Psychiatr Serv 1997;48:1058-63. [59] Ross S, Dermatis H, Levounis P, Galanter M. A Comparison Between Dually Diagnosed Inpatients with and without Axis II Comorbidity and the Relationship to Treatment Outcome. Am J Drug Alcohol Abuse 2003;29:263-79. [60] Chen C, Balogh M, Bathija J, Howanitz E, Plutchik R, Conte H. Substance abuse among psychiatric inpatients. Compr Psychiatry 1992;33:60-4. [61] Kalsa HK, Shaner A, Anglin MD, Wang JC. Prevalence of substance abuse in a psychiatric evaluation unit. Drug Alcohol Depend 1991;28:215-23. [62] Toner BB, Shugar G, Campbell B, Di Gasbarro I. Pattern of substance abuse in psychiatric inpatients. Can J Psychiatry 1991;36:381-3. [63] Wu LT, Gersing K, Burchett B, Woody GE, Blazer DG. Substance use disorders and comorbid Axis I and II psychiatric disorders among young psychiatric patients: Findings from a large electronic health records database. J Psychiatr Res 2011;45:1453-62. [64] Driessen M, Veltrup C, Wetterling T, John U, Dilling H. Axis I and axis II comorbidity in alcohol dependence and the two types of alcoholism. Alcohol Clin Exp Res 1998;22:77-86. [65] Verheul R, Hartgers C, van den Brink W, Koeter MWJ. The effect of sampling, diagnostic criteria and assessment procedures on the observed prevalence of personality disorders in alcoholics. J Stud Alcohol 1998;59:227-36. [66] Morgenstern J, Langenbucher J, Labouvie E, Miller KJ. The comorbidity of alcoholism and personality disorders in a clinical population: prevalence rates and relation to alcohol typology variables. J Abnorm Psychol 1997;106:74-84. [67] Verheul R, van den Brink W, Hartgers C. Prevalence of personality disorders among alcoholics and drug addicts: an overview. Eur Addict Res 1995;1:166-77. [68] Huang Y, Kotov R, de Girolamo G, et al. DSM-IV personality disorders in the WHO World Mental Health Surveys. Br J Psychiatry 2009;195:46-53. [69] Coid J, Yang M, Tyrer P, et al. Prevalence and correlates of personality disorder among adults aged 16 to 74 in Great Britain. Br J Psychiatry 2006;188:423-31. [70] Grant BF, Hasin DS, Stinson FS, et al. Prevalence, correlates, and disability of personality disorders in the United States: results from

[71] [72]

[73]

[74]

[75]

[76]

[77]

[78]

[79]

[80]

[81]

[82]

[83]

[84]

[85]

[86] [87]

[88] [89]

[90]

[91]

the national epidemiologic survey on alcohol and related conditions. J Clin Psychiatry 2004;65:948-58. Berkson J. Limitations of the application of fourfold table analysis to hospital data. Biometrics Bull 1946;2:47-53. Skodol AE, Oldham JM, Gallaher PE. Axis II comorbidity of substance use disorders among patients referred for treatment of personality disorders. Am J Psychiatry 1999;156:733-8. Kokkevi A, Stefanis N, Anastasopoulou E, Kostogianni C. Personality disorders in drug abusers: prevalence and their association with Axis I disorders as predictors of treatment retention. Addict Behav 1998;23:841-53. Brooner RK, King VL, Kidorf M, Schmidt Jr CW, Bigelow GE. Psychiatric and substance use comorbidity among treatment-seeking opioid abusers. Arch Gen Psychiatry 1997;54:71-80. Grilo CM, Martino S, Walker ML, Becker DF, Edell WS, McGlashan TH. Controlled Study of Psychiatric Comorbidity in Psychiatrically Hospitalized Young Adults With Substance Use Disorders. Am J Psychiatry 1997;154:1305-7. Bizzarri JV, Sbrana A, Rucci P, Ravani L, Massei JG, Gonnelli C, et al. The spectrum of substance abuse in bipolar disorder: reasons for use, sensation seeking and substance sensitivity. Bipolar Disord 2007;9:213-20. Dervaux A, Bayle FJ, Laqueille X, Bourdel MC, Le Borgne MH, Oli JP, et al. Is substance abuse in schizophrenia related to impulsivity, sensation seeking, or anhedonia? Am J Psychiatry 2001;158:492-4. Henry C, Bellivier F, Sorbara F, Tangwongchai S, Lacoste J, FaureChaigneau M, et al. Bipolar sensation seeking is associated with a propensity to abuse rather than to temperamental characteristics. Eur Psychiatry 2001;16:289-92. Liraud F, Verdoux H. Which temperamental characteristics are associated with substance use in subjects with psychotic and mood disorders? Psychiatry Res 2000;93:63-72. Kessler RC, Adler L, Barkley R, Biederman J, Conners CK, Demler O, et al. The prevalence and correlates of adult ADHD in the United States: results from the National Comorbidity Survey Replication. Am J Psychiatry 2006;163:716-23. Wilens TE, Biederman J, Kwon A, Ditterline J, Forkner P, Moore H, et al. Risk of substance use disorders in adolescents with bipolar disorder. J Am Acad Child Adolesc Psychiatry 2004;43:1380-6. Conway KP, Swendsen JD, Rounsaville BJ, Merikangas KR. Personality, drug of choice, and comorbid psychopathology among substance abusers. Drug Alcohol Depend 2002;65:225-34. Schubiner H, Tzelepis A, Milberger S, Lockhart N, Kruger M, Kelley BJ, et al. Prevalence of attention-deficit/hyperactivity disorder and conduct disorder among substance abusers. J Clin Psychiatry 2000;61:244-51. Clure C, Brady KT, Saladin ME, Johnson D, Waid R, Rittenbury M. Attention-deficit/hyperactivity disorder and substance use: symptom pattern and drug choice. Am J Drug Alcohol Abuse 1999;25:441-8. Lieberman JA, Kane JM, Alvir J. Provocative tests with psychostimulant drugs in schizophrenia. Psychopharmacology (Berl) 1987;91:415-33. Zubin J, Spring B. Vulnerability – a new view of schizophrenia. J Abnorm Psychol 1977;86:103-26. Schofield D, Tennant C, Nash L, Degenhardt L, Cornish A, Hobbs C, et al. Reasons for cannabis use in psychosis. Aust N Z J Psychiatry 2006;40:570-4. Goswami S, Mattoo SK, Basu D, Singh G. Substance abusing schizophrenics: do they self-medicate? Am J Addict 2004;13:139-50. Bradizza CM, Stasiewicz PR. Qualitative analysis of high risk drug and alcohol use situations among severely mentally ill substance abusers. Addict Behav 2003;28:157-69. Strakowski SM, Del Bello MP, Fleck DE, Arndt S. The impact of substance abuse on the course of bipolar disorder. Biol Psychiatry 2000;48:477-85. Mueser KT, Drake RE, Wallach MA. Dual diagnosis: a review of etiological theories. Addict Behav 1998;23:717-34.

F. Tiziana et al. / Comprehensive Psychiatry xx (2014) xxx–xxx [92] Warner R, Taylor D, Wright J, Sloat A, Springett G, Arnold S, et al. Substance use among mentally ill: prevalence, reasons for use, and effects on illness. Am J Orthopsychiatry 1994;64:30-9. [93] Sivapalan H. Khantzian's 'self-medication hypothesis' of drug addiction and films by Martin Scorsese. Int Rev Psychiatry 2009;21:285-8. [94] Khantzian EJ. The self-medication hypothesis of substance use disorders: a reconsideration and recent applications. Harv Rev Psychiatry 1997;4:231-44. [95] Khantzian EJ. The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependance. Am J Psychiatry 1985;142:1259-64. [96] Cassidy F, Ahearn EP, Carroll BJ. Substance abuse in bipolar disorder. Bipolar Disord 2001;3:181-8. [97] Sherwood Brown E, Suppes T, Adinoff B, Thomas Rajan N. Drug abuse and bipolar disorder: Comorbidity or misdiagnosis? J Affect Disord 2001;65:105-15. [98] Hendrick V, Altshuler LL, Gitlin MJ, Delrahim S, Hammen C. Gender and bipolar illness. J Clin Psychiatry 2000;61:393-6. [99] Kovacs M, Devlin B, Pollock M, Richards C, Mukerji P. A controlled family history study of childhood onset depressive disorder. Arch Gen Psychiatry 1997;54:613-23. [100] Brady KT, Lydiard RB. Bipolar affective disorder and substance abuse. J Clin Psychopharmacol 1992;12(Suppl 1):17-22. [101] Ingraham LJ, Wender PH. Risk for affective disorder and alcohol and other drug abuse in the relatives of affectively ill adoptees. J Affect Disord 1992;26:45-51. [102] Tarter RE, Alterman AI, Edwards KL. Vulnerability to alcoholism in men: a behavior-genetic perspective. J Stud Alcohol 1985;46:329-56. [103] Robinson TE, Berridge KC. Incentive-sensitization and addiction. Addiction 2001;96:103-14. [104] Pontieri FE, Tanda G, Orzi F, Di Chiara G. Effects of nicotine on the nucleus accumbens and similarity to those of addictive drugs. Nature 1996;382:255-7. [105] Di Chiara G, Acquas E, Carboni E. Drug motivation and abuse: a neurobiological perspective. Ann N Y Acad Sci 1992;654:207-19. [106] Cantor-Graae E, Nordstrom LG, McNeil TF. Substance abuse in schizophrenia: A review of the literature and a study of correlates in Sweden. Schizophr Res 2001;48:69-82. [107] Duke PJ, Pantelis C, McPhillips MA, Barnes TR. Comorbid nonalcohol substance misuse among people with schizophrenia: Epidemiological study in central London. Br J Psychiatry 2001;179:509-13. [108] Hansen SS, Munk-Jorgensen P, Guldbaek B, Solgard T, Lauszus KS, Albrechtsen N, et al. Psychoactive substance use diagnoses among psychiatric in-patients. Acta Psychiatr Scand 2000;102:432-8. [109] Lejoyeux M, Boulenguiez S, Fichelle A, McLoughlin M, Claudon M, Ades J. Alcohol dependence among patients admitted to psychiatric emergency services. Gen Hosp Psychiatry 2000;22:206-12. [110] Schiller MJ, Shumway M, Batki SL. Patterns of substance use among patients in an urban psychiatric emergency service. Psychiatr Serv 2000;51:113-5. [111] Menezes PR, Johnson S, Thornicroft G, Marshall J, Prosser D, Bebbington P, et al. Drug and alcohol problems among individuals with severe mental illness in south London. Br J Psychiatry 1996;168:612-9. [112] Thorup A, Petersen L, Jeppesen P, et al. Gender differences in young adults with first-episode schizophrenia spectrum disorders at baseline in the Danish OPUS study. J Nerv Ment Dis 2007;195:396-405. [113] Verdoux H, Mury M, Besançon G, Bourgeois M. Comparative study of substance dependence comorbidity in bipolar, schizophrenic and schizoaffective disorders. Encéphale 1996;22:95-101. [114] Rottanburg D, Robins AH, Ben-Arie O, Teggin A, Elk R. Cannabis-associated psychosis with hypomanic features. Lancet 1982;2:1364-6. [115] Swartz MS, Wagner HR, Swanson JW, et al. Substance use and psychosocial functioning in schizophrenia among new enrollees in the NIMH CATIE study. Psychiatr Serv 2006;57:1110-6.

9

[116] Compton W, Cottler L, Phelps D, et al. Psychiatric disorders among drug dependent subjects: are they primary or secondary? Am J Addict 2000;9:126-34. [117] Kessler R, Crum R, Warner L, et al. Lifetime co-occurrence of DSMIII-R alcohol abuse and dependence with other psychiatric disorders in the national comorbidity survey. Arch Gen Psychiatry 1997;54:313-21. [118] Bonsack C, Camus D, Kaufmann N, Aubert AC, Besson J, Baumann P, et al. Prevalence of substance use in a Swiss psychiatric hospital: Interview reports and urine screening. Addict Behav 2006;31:1252-8. [119] Vaaler AE, Morken G, Flovig JC, Iversen VC, Linaker AM. Substance abuse and recovery in a psychiatric intensive care unit. Gen Hosp Psychiatry 2006;28:65-70. [120] Mueser KT, Yarnold PR, Rosenberg SD, Swett C, Miles KM, Hill D. Substance use disorder in hospitalized severely mentally ill psychiatric patients: Prevalence, correlates, and subgroups. Schizophr Bull 2000;26:179-92. [121] Lambert MT, Griffith JM, Hendrickse W. Characteristics of patients with substance abuse diagnoses on a general psychiatry unit in a VA Medical Center. Psychiatr Serv 1996;47:1104-7. [122] Seedat S, Scott KM, Angermeyer MC, Berglund P, Bromet EJ, Brugha TS, et al. Cross-national associations between gender and mental disorders in the World Health Organization World Mental Health Surveys. Arch Gen Psychiatry 2009;66:785-95. [123] Bobrova N, West R, Malyutina D, Malyutina S, Bobak M. Gender differences in drinking practices in middle aged and older Russians. Alcohol Alcohol 2010;45:573-80. [124] Bloomfield K, Gmel G, Neve R, Mustonen H. Investigating gender convergence in alcohol consumption in Finland, Germany, The Netherlands, and Switzerland: a repeated survey analysis. Subst Abus 2001;22:39-53. [125] Tang AK, Tang WK, Liang HJ, Chan F, Mak SC, Ungvari GS. Clinical Characteristics of Cough Mixture Abusers Referred to Three Substance Abuse Clinics in Hong Kong: A Retrospective Study. East Asian Arch Psychiatry 2012;22:154-9. [126] Reid G, Costigan G. Revisiting ‘The Hidden Epidemic’. A situation assessment of drug use in Asia in the context of HIV/AIDS. Fairfield, AU: Centre for Harm Reduction/Burnet Institute; 2002. [127] Perlick DA, Rosenheck RA, Kaczynski R, Swartz MS, Cañive JM, Lieberman JA. Components and correlates of family burden in schizophrenia. Psychiatr Serv 2006;57:1117-25. [128] Kashner M, Rader L, Rodell D, Beck C, Rodell L, Muller K. Family characteristics, substance abuse, and hospitalization patterns of patients with schizophrenia. Hosp Commun Psychiatry 1991;42:195-7. [129] Niv N, Lopez SR, Glynn SM, Mueser KT. The role of substance use in families, attributions and affective reactions to their relative with severe mental illness. J Nerv Ment Dis 2007;195:307-14. [130] Salyers MP, Mueser KT. Social functioning, psychopathology, and medication side effects in relation to substance use and abuse in schizophrenia. Schizophr Res 2001;48:109-23. [131] Dixon L, McNary S, Lehman A. Substance abuse and family relationships of persons with severe mental illness. Am J Psychiatry 1995;152:456-8. [132] Caton CLM, Shrout PE, Dominguez B, Eagle PF, Opler LA, Cournos F. Risk factors for homelessness among women with schizophrenia. Am J Public Health 1995;85:1153-6. [133] Caton CLM, Shrout PE, Eagle PF, Opler LA, Felix A. Correlates of codisorders in homeless and never homeless indigent schizophrenic men. Psychol Med 1994;24:681-8. [134] Korcha RA, Polcin DL, Kerr WC, Greenfield TK, Bond J. Pressure and help seeking for alcohol problems: trends and correlates from 1984 to 2005. Addict Behav 2013;38:1740-6. [135] Fazel M, Wheeler J, Danesh J. Prevalence of serious mental disorder in 7000 refugees resettled in western countries: a systematic review. Lancet 2005;15:1309-14.

10

F. Tiziana et al. / Comprehensive Psychiatry xx (2014) xxx–xxx

[136] Andersen RM. Revisiting the behavioral model and access to medical care: does it matter? J Health Soc Behav 1995;36:1-10. [137] Andersen R, Newman JF. Societal and individual determinants of medical care utilization in the United States. Milbank Mem Fund Q Health Soc 1973;51:95-124. [138] Amore M, Menchetti M, Tonti C, Scarlatti F, Lundgren E, Esposito W, et al. Predictors of violent behavior among acute psychiatric patients: clinical study. Psychiatry Clin Neurosci 2008;62:247-55.

[139] Ries RK, Russo J, Wingerson D, Snowden M, Comtois KA, Srebnik D, et al. Shorter hospital stays and more rapid improvement among patients with schizophrenia and substance disorders. Psychiatr Serv 2000;51:210-5. [140] Xiong Lai HM, Sitharthan T. Exploration of the Comorbidity of Cannabis Use Disorders and Mental Health Disorders among Inpatients Presenting to All Hospitals in New South Wales Australia. Am J Drug Alcohol Abuse 2012;38:567-74.