ORIGINAL ARTICLE
Predictors of Persistent Psychotic Symptoms in Persons With Methamphetamine Abuse Receiving Psychiatric Treatment Tania Lecomte, PhD,* Kim T. Mueser, PhD,Þ William MacEwan, MD,þ Allen E. Thornton, PhD,§ Tari Buchanan, BA,þ Vanessa Bouchard, MSc,* Elliot Goldner, MD,|| Johann Brink, MD,þ Donna Lang, PhD,¶ Shimi Kang, MD,þ Alasdair M. Barr, PhD,L and William G. Honer, MDþ Abstract: The objective of this study was to identify predictors of sustained psychotic symptoms after methamphetamine (MA) abuse during the course of 6 months from patterns of MA and other substance use, depressive symptoms, family history of psychosis, antisocial personality disorder, and trauma history. A total of 295 individuals with MA abuse and psychotic symptoms seeking psychiatric services were assessed at baseline and then monthly on symptoms and substance use for 6 months. Trajectory analyses revealed two trajectories of the individuals with positive symptoms, with one group presenting with persistent psychotic symptoms (30% of the sample). Those with persistent psychosis were significantly older, had more severe psychotic symptoms, misused MA for more years, had more antisocial personality traits, and had more sustained depressive symptoms. The strongest predictors of belonging to the persistent psychosis group, via logistic regressions, were more severe psychotic symptoms, longer use of MA, and sustained depressive symptoms. Our results highlight the important comorbidities, especially regarding depressive symptoms and persistent psychosis, in individuals seeking psychiatric help after MA abuse. This study also highlights the importance of identifying people with persistent psychosis within MA users to facilitate rapid and effective treatment of co-occurring psychotic disorder. Key Words: Psychosis, methamphetamine, depression, dual disorder (J Nerv Ment Dis 2013;201: 1085Y1089)
M
ethamphetamine (MA) abuse is a persistent problem for many adults and youths across the globe (World Health Organization, 1997). Psychosocial effects of the drug include personality changes; legal problems; at-risk behaviors; and high societal costs such as loss of family support, housing instability, and hospitalizations. Multiple studies have demonstrated the toxicity of MA on the brain, suggesting long-term damaging consequences on cognitive abilities and mental health (see review; Barr et al., 2006). Studies suggest that up to two thirds of long-term MA users experience psychotic symptoms during intoxication (McKetin et al., 2006), of
*De´partement de Psychologie, Universite´ de Montre´al, Montreal, Quebec, Canada; †Center for Psychiatric Rehabilitation, Boston University, Massachusetts; ‡Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; §Department of Psychology, and; ||Faculty of Health Sciences, University of Simon Fraser, Burnaby, British Columbia, Canada; ¶Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada; and LDepartment of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada. Presented in part at the Schizophrenia International Research Society, Florence, Italy, April 14, 2010, and at the International Congress on Schizophrenia Research (ICOSR), Colorado Springs, April 4, 2011. This study took place in Vancouver, Burnaby, and South Fraser, British Columbia, Canada. Send reprint requests to Tania Lecomte, PhD, De´partement de Psychologie, Universite´ de Montre´al, Pavillon Marie-Victorin, Bur C-358, 90 rue Vincent d’Indy, C.P. 6128, Succ. Centre-Ville, Montreal, Quebec, H3C 3J7, Canada. E-mail: [email protected]. Copyright * 2013 by Lippincott Williams & Wilkins ISSN: 0022-3018/13/20112Y1085 DOI: 10.1097/NMD.0000000000000059
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whom 64% experience persistent psychotic symptoms for more than 10 days after the cessation of MA use (Yui et al., 2002b), and 21% have psychotic symptoms for more than 6 months (Yui et al., 2002a). Among people whose MA-induced psychosis remits and who stop using, almost half have a spontaneous recurrence of psychotic symptoms during the following year (Yui et al., 2002a). MA users with persistent or recurrent psychotic symptoms are vulnerable to stress and may benefit from antipsychotic medication the same way individuals with schizophrenia do (Yui et al., 2002a). Although long-term MA abuse can lead to persistent psychotic symptoms, MA can also trigger psychotic symptoms in people vulnerable to psychosis. Lifetime MA abuse by individuals with a psychotic disorder ranges from 21% to 33% (Bu¨hler et al., 2002; Fowler et al., 1998; Mueser et al., 1990b; Pacific Community Resources, 2002), and drug abuse, particularly stimulant abuse, is associated with an earlier age at first hospitalization for schizophrenia (Bu¨hler et al., 2002; Hambrecht and Ha¨fner, 1996; Mueser et al., 1990a); more severe symptoms; and more problems in interpersonal relationships, motivation, role functioning, and activities (Addington and Addington, 1998). Although transient psychotic symptoms induced by MA may have distinguishing features such as paranoia, panic, hyperactivity, vivid auditory hallucinations, and obsessive-compulsive behaviors, persistent psychotic symptoms after MA abuse tend to be undistinguishable from those found in schizophrenia (Srisurapanont et al., 2011). Furthermore, Mikami et al. (2003) describe identical eyemovement dysfunction in individuals with persistent psychotic symptoms after MA abuse and in individuals with schizophrenia. Widespread MA use in North America is a fairly recent phenomenon, and therefore, little is known about the profiles of individuals whose MA-induced psychotic symptoms persist compared with those who experience temporary psychotic symptoms. Several risk factors are associated with the development of more severe or sustained psychosis after MA ingestion. Injection MA use increases the risk for developing more persistent psychotic symptoms compared with other routes of administration, such as inhalation and swallowing (Yui et al., 2002a, 2002b), as does binge use (e.g., daily use of MA for several days), compared with low dose daily or occasional use (Chen et al., 2003). Polysubstance abuse may also be associated with an increased risk for persistent psychotic disorders (Bretch et al., 2004; Halkitis, 2009). Other less investigated possible predictors of persistent psychosis in MA abusers have been suggested, including familial history of psychosis (Chen et al., 2005), antisocial personality traits, more severe depressive symptoms, and alcohol dependence (Chen et al., 2003). In mice, an enriched environment can protect from some of the negative effects of MA by preventing neurotoxicity and decreasing responsiveness to the drug (Bezard et al., 2003), suggesting that a negative environment, such as childhood trauma, could increase the risk for experiencing negative consequences from using MA, such as persistent psychotic symptoms. Trauma history is a risk factor for both substance abuse and schizophrenia (Cutajar et al., 2010), although it is not clear whether trauma exposure is related to the development of persistent psychotic symptoms after MA use.
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More research is needed to identify which individuals who experience psychotic symptoms after MA use have persistent symptoms to inform treatment of both their addiction and psychosis (Drake et al., 1998, 2004; Mueser et al., 2003). Other than a few case reviews suggesting the efficacy of electroconvulsive therapy (Grelotti et al., 2010) or of antipsychotic medication (Dore and Sweeting, 2006) for treating psychosis in MA users, the MA treatments investigated in North America so far have used an ‘‘addiction’’ treatment model for stimulant dependence that has not addressed comorbid mental health problems such as persistent psychotic symptoms (Cretzmeyer et al., 2003; Rawson et al., 2002; Reiber et al., 2000). To offer services that target the specific needs of individuals with persistent psychotic symptoms, a more thorough understanding of symptomatic profiles and of specific risk factors is warranted (Barr et al., 2006). The objective of this study was to identify the predictors of sustained psychotic symptoms after initial treatment of MA-related psychotic symptoms during the course of a 6-month follow-up period. The predictors included sociodemographic characteristics, patterns of MA use and other substance use, family history of psychosis, trauma history, antisocial personality traits, and depressive symptoms. On the basis of the extant literature, we hypothesized that persistent psychotic symptoms would be associated with a) more severe abuse of MA and other substances, b) family history of psychosis, c) more trauma exposure, d) antisocial personality disorder (ASPD) traits, and e) more severe depression.
METHODS This was a longitudinal study with a comprehensive battery of tests administered at baseline and 6-month follow-up and specific substance abuse and clinical measures administered monthly for 6 months. Demographic characteristics, family history of psychosis, history of substance abuse, trauma exposure, and antisocial personality traits were evaluated only at baseline. This study took place in Vancouver, British Columbia, from November 2005 until April 2011.
Participants A total of 295 participants were recruited. The inclusion criteria for this study were 18 years or older; MA use disorderVas defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; presence of psychotic symptoms (four or more on hallucinations and/or unusual thought content on the Brief Psychiatric Rating ScaleYExpanded [BPRS-E; Ventura et al., 1993] within the last 2 weeks after MA ingestion); and less than 2 years since the initial diagnosis of MA-induced psychosis. The only exclusion criterion was inability to communicate in English. Two approaches to recruitment were used. First, 121 participants were approached after being admitted to the psychiatric emergency department of a collaborating hospital (Vancouver General Hospital, St. Paul’s Hospital, Children and Women’s Hospital, Riverview Hospital, or the Forensic Psychiatric Institute) because of florid psychotic symptoms. Second, 174 participants were recruited by a psychiatrist (W. M) who provided services in shelters, special housing for homeless individuals, or community organizations serving individuals with substance use problems (e.g., the Portland Hotel Society, Princess Rooms, Dodson and Jubilee Rooms, Dr. Peter Centre, and Directions). All necessary ethical approvals were obtained, and informed consent was carefully observed. Informed consent was determined by administering a 10-item true-false questionnaire about this study to the participants; those who did not obtain a perfect score after three trials were not allowed to participate (everyone succeeded). 1086
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Measures The participants completed two interviews for the baseline assessment and one for each monthly assessment and received a small stipend for their time. A self-report questionnaire was used to obtain information about age, sex, education, housing, concerns about illness, past diagnoses, and reasons for using MA. Substance use was assessed with the brief Addiction Severity Index (ASI; Zanis et al., 1997) and the Time-Line Follow-Back (TLFB; Sobell et al., 1980). The brief ASI assesses frequencies and quantities of psychoactive substances used, as well as impact (e.g., overdose). The TLFB elicits a specific week-by-week recollection of alcohol and drug use during the past month. Four measures of MA use were computed for each monthly assessment, including number of days used, number of grams ingested, method of ingestion (injected or other), and presence/absence of binging (93 days in a week using more than 1 g of MA). These four scores across all 6 months were summed to form total scores. For polysubstance abuse, a monthly score consisting of the number of different drugs used was calculated. Family history of psychosis was assessed using the screening questions from the Family Interview for Genetic Studies (Tsuang, 1994), which includes 15 questions (yes/no or don’t know) regarding the presence of family members who had behaviors, symptoms, or a diagnosis of a mental illness. The BPRS-E (Ventura et al., 1993) was used to determine psychosis at entry into this study and at every monthly time point. The 24-item semistructured interview was conducted by trained interviewers, following the guidelines from the University of California at Los Angeles. Depression was assessed monthly with the Beck Depression InventoryYII (Beck et al., 1996), which has 21 items and for which a score greater than 13 is considered clinically significant for mild depression; greater than 20, for moderate depression; and greater than 28, for severe depression (Beck et al., 1996). The mean score during the course of the 6 months of this study was used here. The Brief Trauma Questionnaire (BTQ; Schnurr et al., 1999) was administered to assess trauma exposure. The BTQ contains 10 simple yes/no questions, 3 of which assess childhood trauma, and has been extensively validated, including individuals with co-occurring disorders (Mueser et al., 2001). The Antisocial Personality Disorder Scale was used at baseline, which is a structured interview based on the Structured Clinical Interview for DSM-IV, Axis II (First et al., 1997), used to ascertain ASPD traits and diagnosis and including childhood conduct disorder.
Analyses Trajectory analyses were used to identify significantly distinct subgroups of participants on the basis of the pattern of their psychotic symptoms during the 6-month period. The psychotic symptom score used at each time point was the six-item BPRS positive symptom scale. The trajectory analyses were conducted using the SAS Proc Traj procedure developed by Jones et al. (2001). The procedure uses mixture models for estimating developmental trajectories, enabling one to identify the number and the polynomial form of different trajectories present in a sample, as well as offering the probability of each subject belonging to an identified trajectory. The end solution regarding the number and the form of trajectories is the one that minimizes the Akaike’s information criteria. Following this, each subject is assigned to the most probable trajectory. Similar to cluster analysis, the trajectory analysis groups individuals rather than variables. The SAS Proc Traj procedure assumes that data are missing at random and therefore includes all the subjects in the analyses. To identify potential predictors of persistent psychosis, the trajectories were then compared with the Pearson’s chi-square tests for categorical variables and with the Student’s t-tests for continuous variables. The significant variables were then entered into a logistic regression, using Forward Wald, to * 2013 Lippincott Williams & Wilkins
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Psychotic Symptoms in MA Abuse
FIGURE 1. Individuals’ trajectories during this study on the BPRS positive symptoms.
determine which predictors most uniquely predicted the persistent psychosis trajectory.
RESULTS Of the 295 participants assessed at baseline, 223 were included in the trajectory analysis because they had completed assessments for at least two time points, excluding the baseline. Given that one of the inclusion criteria for this study was high psychotic symptoms, we did not include the baseline BPRS score for positive symptoms in the analysis. Of the 295 initially included in this study, 158 could be contacted for the 6-month assessment. Those who did not complete the last assessment were significantly younger (t[201] = 2.66, p G 0.05; mean, 30.9; SD, 11.1 vs. mean, 35.5; SD, 10.3), had more
severe psychiatric symptoms (but not specifically psychotic symptoms; t[221] = 2.34, p G 0.05), used smaller quantities of MA at baseline (t[173] = 1.79, p G 0.05), and were less likely to inject MA (t[221] = 2.2, p G 0.05). The trajectory analyses generated two groupsVone with lower psychotic symptoms (70.2%, n = 157) and one with more persistent psychotic symptoms (29.8%, n = 66; see Figure 1; see Table 1 for demographic and clinical characteristics of each trajectory group). Comparisons of the two groups on baseline characteristics indicated that those with persistent psychotic symptoms were significantly older (see Table 1), had higher baseline psychotic symptoms (t[221] = 1.57, p G 0.001), had higher baseline depressive symptoms (t[221] = 4.09, p G 0.001), and had higher baseline overall
TABLE 1. Sociodemographic and Clinical Characteristics of the Low Psychosis and Persistent Psychosis Trajectory Groups Low/Persistent Psychosis Variables (n)/Category
Sex (n = 223)/male Age (n = 203) Education (n = 203) Birth country (n = 223)/Canada Family history of psychosis (n = 183) No. years of MA use (n = 222) No. years of regular alcohol use (n = 222) No. years of cannabis use (n = 222) Total no. days of MA use (n = 191) Total no. grams of MA useda (n = 191) MA injection scoreb (n = 221) No. substances used (n = 219) Binge scorec (n = 219) ASPD traits (n = 217) Met the criteria for ASPD Childhood trauma score (n = 220) Total trauma exposure Total BDI score (n = 221) Total BPRS total score (n = 221)
Mean (SD) or n (%)
111 (73%) 32.90 (10.83) 10.64 (2.30) 141 (89%) 52 (38.8%) 4.11 (5.29) 6.12 (7.41) 10.47 (9.68) 50.09 (51.31) 4.96 (6.87) 5.49 (8.09) 4.72 (2.09) 1.98 (1.81) 20.96 (3.79) 81 (54%) 1.36 (1.27) 8.96 (4.79) 11.20 (7.69) 36.07 (12.99)
46 (69%) 38.11 (9.60) 10.80 (2.53) 60 (94%) 23 (46.9%) 6.58 (8.00) 9.29 (11.44) 13.46 (12.34) 49.02 (47.16) 4.10 (4.62) 4.94 (7.00) 4.98 (2.21) 1.75 (1.79) 22.13 (4.29) 44 (69%) 1.26 (1.34) 9.05 (4.87) 15.66 (9.18) 46.88 (19.47)
Statistical Test
Significance
W = 2.41 t = j3.14 t = j0.41 W2 = 10.33 W2 = 1.85 t = j2.29 t = j2.07 t = j1.75 t = 0.14 t = 0.14 t = 0.48 t = j0.06 t = 0.87 t = j1.98 W2 = 5.04 t = 0.48 t = j0.12 t = j3.43 t = j4.09
p = 0.30 p = 0.002* p = 0.69 p = 0.67 p = 0.76 p = 0.02* p = 0.04* p = 0.08 p = 0.89 p = 0.89 p = 0.63 p = 0.95 p = 0.38 p = 0.05* p = 0.08 p = 0.64 p = 0.91 p = 0.001** p = 0.000**
2
a
Range, 0.03 to 38 g. Score calculated in number of weeks MA was injected during the study. For each month of this study, a score of 1 was given if a person used more than 1 g of MA during a binge (minimum of 3 days in a row). *p G .05. **p G .001. b c
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symptoms (t[221] = 7.77, p G 0.001). No differences were found in terms of baseline negative symptoms (p = 0.42). The persistent psychosis trajectory group had been using MA and alcohol for significantly more years. There were significantly more individuals in the persistent psychosis group with ASPD traits, although only a trend in terms of an ASPD diagnosis. No significant differences were found for family history of psychosis or childhood trauma. In terms of continuous measures taken during this study, those who were more depressed across the time points were also more likely to be in the persistent psychosis trajectory group. No significant differences were found between the groups on any of the measures of MA use during the 6-month study period (days, grams, injection, and binging) or for polysubstance abuse. Among the baseline variables, logistic regression indicated that the most significant predictors of persistent psychotic symptoms were having high baseline psychotic symptoms (odds ratio, 12.04; 95% confidence interval [CI], 3.53Y12.04) and having used MA for more years (odds ratio, 1.18; 95% CI, 0.99Y1.18). As for the continuous variables collected during this study, high depression scores on the BDI during the course of 6 months was the sole predictor of being in the persistent psychosis group (odds ratio, 3.43; 95% CI, 1.74Y6.76, p G 0.001).
DISCUSSION The purpose of this study was to determine the profiles of individuals with more sustained psychotic symptoms after MA abuse. We found a slightly higher proportion of MA users whose psychotic symptoms persisted over time than those in the study of Yui et al. (2002b), 30% vs. 21%, respectively. Two factors that may have contributed to the higher percentage of people with persistent psychosis in this sample were that all users were living in the community and not abstinent of drugs or incarcerated, in contrast to the study of Yui et al. (2002b), and the users had longer exposure to MA (6 years vs. 8 months, respectively), suggesting that longer use of MA is associated with persistent psychosis. Contrary to the study of Chen et al. (2005), we did not find an association between family history of psychosis and persistent psychosis, although 23% of our sample reported having a family member with psychosis. Rather, the individuals who experienced persistent psychosis were older and long-time MA users with more severe initial psychotic symptoms and depression than those with transient psychosis. Similar findings have been reported elsewhere with an abstinent sample (Lichlyter et al., 2011). Although family history of psychosis was not predictive of persistent psychosis after MA use, direct family interviews were not conducted, and thus, our results do not rule out increased vulnerability to schizophrenia as a contributing factor, as suggested by Mikami et al. (2003). Given that more years of MA abuse were linked to higher likelihood of having sustained psychotic symptoms, the findings somewhat support the neurotoxicity model whereby long-term MA abuse can alter the dopamine system, resulting in more severe and more persistent psychotic symptoms similar to those found in untreated schizophrenia (Barr et al., 2006). In our study, severity of depression during the 6-month follow-up period was the second strongest predictor of sustained psychotic symptoms, after initial psychosis severity. Depression is common in individuals with MA dependence without psychosis, with rates varying from 13% (Salo et al., 2011) to as high as 64% (Conway et al., 2006). In the MA users with concurrent psychotic symptoms in this sample, the rates were even higher, with 67% scoring as clinically depressed at baseline (Lecomte et al., 2010). Extensive research documents that psychosis and depression are strongly linked, with depression being a consistent syndrome across the long-term course of schizophrenia (Ha¨fner et al., 2008). Furthermore, individuals with major depression have even more severe depression when psychotic symptoms are also present (Gaudiano et al., 2009). 1088
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The finding that individuals with persistent psychosis had more antisocial behavior traits might be linked to the fact that more severe substance abuse is associated with antisocial traits, which, in turn, could lead to more damaging consequences on mental health and quality of life (Mueser et al., 2006). It could also be explained by early social isolation caused by disruptive childhood conduct behaviors, leading to a poorer social network that is unlikely to help when someone starts becoming psychotic. This result reflects the sample of individuals seeking psychiatric help in our studyVmost were polysubstance users, living in the margin of society as indicated by low employment and unstable housing (Lecomte et al., 2010)V and for whom many ‘‘antisocial’’ behaviors are considered survival behaviors on the streets. Polysubstance abuse and childhood abuse were not more prevalent in either psychosis subgroup but were highly prevalent in the sample as a whole (96% and 56%, respectively), also reflecting the important comorbidities found in our sample. We were unable to specifically look at childhood sexual abuse, increasingly reported as being linked to psychosis (Bendall et al., 2008), given that the trauma measure used (BTQ) has questions on sexual assault but not according to age. We were also intrigued by the mean age of our sample, which was older than what we had anticipated. In fact, it seems that MA appeals not only to young individuals but also to more experienced drug users, given the low cost and the rapid intoxicating effects. One limitation of this study was the significant attrition of the participants at the 6-month follow-up, with only 54% of the sample available for assessment, although 76% of the sample was evaluated for at least two follow-up assessments. Contrary to many other studies that focused on single-drug users and excluded individuals with previous psychiatric diagnoses, our sample was more ecologically representative of the individuals who abuse MA and who seek psychiatric help for psychotic symptoms. As such, we cannot infer that the psychotic symptoms were linked to only MA abuse, and a primary psychosis may have been present in some users, although MA was considered the drug of choice for most of our sample (Lecomte et al., 2010). This study found that among treatment-seeking MA users with psychotic symptoms, persistent psychosis was associated with older age, more years of MA and alcohol abuse, and presentation of more severe psychotic and depressive symptoms. More work is needed to develop treatment programs that target the special needs of people with co-occurring MA addiction and psychosis. The present study takes a step toward accomplishing this by identifying individuals with MA-induced psychosis whose psychotic symptoms are likely to persist and who are most likely to benefit from comprehensive treatment designed to integrate the management of the psychiatric symptoms with treatment of the addiction. ACKNOWLEDGMENTS The authors thank the participants from Vancouver, Burnaby, and South Fraser who took part in this project as well as the research assistants, the clinicians, and the MARC members who helped along the way. DISCLOSURES This research was supported by two Canadian Institute of Health Research (CIHR) grants as well as by the Provincial Health Services Authorities of British Columbia. The first author was a CIHR and Michael Smith Foundation award recipient during this study. The authors declare no conflict of interest. REFERENCES Addington J, Addington D (1998) Effect of substance misuse in early psychosis. Br J Psychiatry Suppl. 172:134Y136.
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Barr AM, Panenka WJ, MacEwan GW, Thornton AE, Lang DM, Honer WG, Lecomte T (2006) The need for speed: An update on methamphetamine addiction. J Psychiatry Neurosci. 31:301Y313. Beck AT, Steer RA, Ball R, Ranieri W (1996) Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients. J Pers Assess. 67:588Y597. Bendall S, Jackson HJ, Hulbert CA, McGorry PD (2008) Childhood trauma and psychotic disorders: A systematic, critical review of the evidence. Schizophr Bull. 34:568Y569. Bezard E, Dovero S, Belin D, Duconger S, Jackson-Lewis V, Przedborski S, Jaber M (2003) Enriched environment confers resistance to 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine and cocaine: Involvement of dopamine transporter and trophic factors. J Neurosci. 23:1099Y11007. Bretch M-L, O’Brien A, von Mayrhauser C, Anglin MD (2004) Methamphetamine use behaviors and gender differences. Addict Behav. 29:89Y106. Bu¨hler B, Hambrecht M, Lo¨ffler W, An der Heiden W, Ha¨fner H (2002) Precipitation and determination of the onset and course of schizophrenia by substance abuseVA retrospective and prospective study of 232 population-based first illness episodes. Schizophr Res. 54:243Y251. Chen C-K, Lin S-K, Sham PS, Ball SD, Loh E-W, Hsiao C-C, Murray RM (2003) Pre-morbid characteristics and co-morbidity of methamphetamine users with and without psychosis. Psychol Med. 33:1407Y1414. Chen CK, Lin SK, Sham PK, Ball D, Loh EW, Murray RM (2005) Morbid risk for psychiatric disorder among the relatives of methamphetamine users with and without psychosis. Am J Med Genet B Neuropsychiatr Genet. 136B:87Y91. Conway KP, Compton W, Stinson FS, Grant BF (2006) Lifetime comorbidity of DSM-IV mood and anxiety disorders and specific drug use disorders: Results from the National Epidemiologic Survey on Alcohol and Related Conditions. J Clin Psychiatry. 67:247Y257. Cretzmeyer M, Vaughan Sarrazin M, Huber DL, Block RI, Hall JA (2003) Treatment of methamphetamine abuse: Research findings and clinical directions. J Subst Abuse Treat. 24:267Y277. Cutajar MC, Mullen PE, Ogloff JR, Thomas SD, Wells DL, Spataro J (2010) Psychopathology in a large cohort of sexually abused children followed up to 43 years. Child Abuse Negl. 34:813Y822. Dore G, Sweeting M (2006) Drug-induced psychosis associated with crystalline methamphetamine. Australas Psychiatry. 14:86Y89. Drake R, Mercer-McFadden C, Mueser KT, McHugo G, Bond GR (1998) Review of integrated mental health and substance abuse treatment for patients with dual disorders. Schizophr Bull. 24:589Y607. Drake R, Mueser KT, Brunette MF, McHugo G (2004) A review of treatments for patients with severe mental illness and co-occuring substance use disorders. Psychiatr Rehabil J. 27:360Y374. First MB, Spitzer RL, Gibbon M, Williams JBW (1997) Structured clinical interview for DSM-IV axis I and II disordersVPatient edition. New York: Biometrics Research Department. Fowler IL, Carr VJ, Carter NT, Lewin TJ (1998) Patterns of current and lifetime substance use in schizophrenia. Schizophr Bull. 24:443Y455. Gaudiano BA, Dalrymple KL, Zimmerman M (2009) Prevalence and clinical characteristics of psychotic versus nonpsychotic major depression in a general psychiatric outpatient clinic. Depress Anxiety. 26:54Y64. Grelotti DJ, Kanayama G, Pope HG Jr (2010) Remission of persistent methamphetamine-induced psychosis after electroconvulsive therapy: Presentation of a case and review of the literature. Am J Psychiatry. 167:17Y23. doi:10.1176/appi.ajp.2009.08111695. Ha¨fner H, an der Heiden W, Maurer K (2008) Evidence for separate diseases?: Stages of one disease or different combinations of symptom dimensions? Eur Arch Psychiatry Clin Neurosci. 258(suppl 2):85Y96. Halkitis PN (2009) Methamphetamine addiction. Washington, DC: American Psychological Association. Hambrecht M, Ha¨fner H (1996) Substance abuse and the onset of schizophrenia. Biol Psychiatry. 40:1155Y1163. Jones BL, Nagin DS, Roeder K (2001) A SAS procedure based on mixture models for estimating developmental trajectories. Sociol Methods Res. 29:374Y393. Lecomte T, Mueser KT, MacEwan WG, Laferrie`re-Simard M-C, Thornton AE, Buchanan T, Honer WG (2010) Profiles of individuals seeking psychiatric
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help for psychotic symptoms linked to methamphetamine abuseVBaseline results from the MAPS (Methamphetamine and Psychosis Study). Ment Health Subst Use Dual Diagn. 3:168Y181. Lichlyter B, Purdon S, Tibbo P (2011) Predictors of psychosis severity in individuals with primary stimulant addictions. Addict Behav. 36:137Y139. McKetin R, McLaren J, Lubman DI, Hides L (2006) The prevalence of psychotic symptoms among methamphetamine users. Addiction. 101:1473Y1478. Mikami T, Naruse N, Fukura Y, Ohkubo H, Ohkubo T, Matsuura M, Kojima T (2003) Determining vulnerability to schizophrenia in methamphetamine psychosis using exploratory eye movements. Psychiatry Clin Neurosci. 57:433Y440. doi:10.1046/j.1440-1819.2003.01143.x. Mueser KT, Frisman LB, Drake R, Covell NH, Essock SM (2006) Conduct disorder and antisocial personality disorder in persons with severe psychiatric and substance use disorders. Schizophr Bull. 32:626Y636. Mueser KT, Noordsy DL, Drake RE, Fox LB (2003) Integrated treatment for dual disordersVA guide to effective practice. New York: The Guilford Press. Mueser KT, Salyers MP, Rosenberg SD, Ford JD, Fox L, Cardy P (2001) A psychometric evaluation of trauma and PTSD assessments in persons with severe mental illness. Psychol Assess. 13:110Y117. Mueser KT, Yarnold PR, Levinson DF, Singh H, Bellack AS, Kee K, Yadalam KG (1990a) Prevalence of substance abuse in schizophrenia: Demographic and clinical correlates. Schizophr Bull. 16:31Y56. Mueser KT, Yarnold PR, Levinson DF, Singh H, Bellack AS, Kee K, Yadalam KG (1990b) Prevalence of substance abuse in schizophrenia: Demographic and clinical correlates. Schizophr Bull. 16:31Y56. PCR (2002) Lower mainland youth drug survey. Surrey, Canada: Pacific Community Resources. Rawson R, Gonzales R, Brethen P (2002) Treatment of methamphetamine use disorders: An update. J Subst Abuse Treat. 23:145Y150. Reiber C, Galloway GP, Cohen J, Hsu JC, Lord RH (2000) A descriptive analysis of participant characteristics and patterns of substance use in the CSAT methamphetamine treatment project: The first six months. J Psychoactive Drugs. 32:183Y191. Salo R, Flower K, Kielstein A, Leamon M, Nordahl TE, Galloway GP (2011) Psychiatric comorbidity in methamphetamine dependence. Psychiatry Res. 186:356Y361. Schnurr PP, Vielhauer MJ, Weathers F, Findler M (1999) The Brief Trauma Questionnaire. White River Junction, VT: National Center for PTSD. Sobell MB, Maisto SA, Sobell LC, Copper AM, Sanders B (1980) Developing a prototype for evaluating alcohol treatment effectiveness. In Sobell LC, Sobell MB, Ward E (Eds), Evaluating alcohol and drug abuse treatment effectiveness (pp 129Y150). New York: Pergamon Press. Srisurapanont M, Arunpongpaisal S, Wada K, Marsden J, Ali R, Kongsakon R (2011) Comparisons of methamphetamine psychotic and schizophrenic symptoms: A differential item functioning analysis. Prog Neuropsychopharmacol Biol Psychiatry. 35:959Y964. Tsuang MT (1994) Genetics, epidemiology, and the search for causes of schizophrenia. Am J Psychiatry. 151:3Y6. Ventura J, Green M, Shaner A, Liberman RP (1993) Training and quality assurance with the Brief Psychiatric Rating Scale. Int J Methods Psychiatr Res. 3:221Y244. World Health Organization (1997) World Health Organization. Amphetaminelike stimulants: A report from the WHO meeting an amphetamines, MDMA and other psychostimulants. Geneva, Switzerland: Substance Abuse Department, WHO. Yui K, Ikemoto S, Goto K, Nishijima K, Yoshino T, Ishiguro T (2002a) Spontaneous recurrence of methamphetamine-induced paranoid-hallucinatory states in female subjects: Susceptibility to psychotic states and implications for relapse of schizophrenia. Pharmacopsychiatry. 35:62Y71. Yui K, Ikemoto S, Ishiguro T, Goto K (2002b) Factors for susceptibility to episode recurrence in spontaneous recurrence of methamphetamine psychosis. Ann N Y Acad Sci. 965:292Y304. Zanis DA, McLellan A, Thomas CS (1997) Is the Addiction Severity Index a reliable and valid assessment instrument among clients with severe and persistent mental illness and substance abuse disorders? Community Ment Health J. 33:213Y227.
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Predictors of Persistent Psychotic Symptoms in Persons With Methamphetamine Abuse Receiving Psychiatric Treatment Tania Lecomte, PhD,* Kim T. Mueser, PhD,Þ William MacEwan, MD,þ Allen E. Thornton, PhD,§ Tari Buchanan, BA,þ Vanessa Bouchard, MSc,* Elliot Goldner, MD,|| Johann Brink, MD,þ Donna Lang, PhD,¶ Shimi Kang, MD,þ Alasdair M. Barr, PhD,L and William G. Honer, MDþ Abstract: The objective of this study was to identify predictors of sustained psychotic symptoms after methamphetamine (MA) abuse during the course of 6 months from patterns of MA and other substance use, depressive symptoms, family history of psychosis, antisocial personality disorder, and trauma history. A total of 295 individuals with MA abuse and psychotic symptoms seeking psychiatric services were assessed at baseline and then monthly on symptoms and substance use for 6 months. Trajectory analyses revealed two trajectories of the individuals with positive symptoms, with one group presenting with persistent psychotic symptoms (30% of the sample). Those with persistent psychosis were significantly older, had more severe psychotic symptoms, misused MA for more years, had more antisocial personality traits, and had more sustained depressive symptoms. The strongest predictors of belonging to the persistent psychosis group, via logistic regressions, were more severe psychotic symptoms, longer use of MA, and sustained depressive symptoms. Our results highlight the important comorbidities, especially regarding depressive symptoms and persistent psychosis, in individuals seeking psychiatric help after MA abuse. This study also highlights the importance of identifying people with persistent psychosis within MA users to facilitate rapid and effective treatment of co-occurring psychotic disorder. Key Words: Psychosis, methamphetamine, depression, dual disorder (J Nerv Ment Dis 2013;201: 1085Y1089)
M
ethamphetamine (MA) abuse is a persistent problem for many adults and youths across the globe (World Health Organization, 1997). Psychosocial effects of the drug include personality changes; legal problems; at-risk behaviors; and high societal costs such as loss of family support, housing instability, and hospitalizations. Multiple studies have demonstrated the toxicity of MA on the brain, suggesting long-term damaging consequences on cognitive abilities and mental health (see review; Barr et al., 2006). Studies suggest that up to two thirds of long-term MA users experience psychotic symptoms during intoxication (McKetin et al., 2006), of
*De´partement de Psychologie, Universite´ de Montre´al, Montreal, Quebec, Canada; †Center for Psychiatric Rehabilitation, Boston University, Massachusetts; ‡Department of Psychiatry, University of British Columbia, Vancouver, British Columbia, Canada; §Department of Psychology, and; ||Faculty of Health Sciences, University of Simon Fraser, Burnaby, British Columbia, Canada; ¶Department of Radiology, University of British Columbia, Vancouver, British Columbia, Canada; and LDepartment of Anesthesiology, Pharmacology & Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada. Presented in part at the Schizophrenia International Research Society, Florence, Italy, April 14, 2010, and at the International Congress on Schizophrenia Research (ICOSR), Colorado Springs, April 4, 2011. This study took place in Vancouver, Burnaby, and South Fraser, British Columbia, Canada. Send reprint requests to Tania Lecomte, PhD, De´partement de Psychologie, Universite´ de Montre´al, Pavillon Marie-Victorin, Bur C-358, 90 rue Vincent d’Indy, C.P. 6128, Succ. Centre-Ville, Montreal, Quebec, H3C 3J7, Canada. E-mail: [email protected]. Copyright * 2013 by Lippincott Williams & Wilkins ISSN: 0022-3018/13/20112Y1085 DOI: 10.1097/NMD.0000000000000059
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whom 64% experience persistent psychotic symptoms for more than 10 days after the cessation of MA use (Yui et al., 2002b), and 21% have psychotic symptoms for more than 6 months (Yui et al., 2002a). Among people whose MA-induced psychosis remits and who stop using, almost half have a spontaneous recurrence of psychotic symptoms during the following year (Yui et al., 2002a). MA users with persistent or recurrent psychotic symptoms are vulnerable to stress and may benefit from antipsychotic medication the same way individuals with schizophrenia do (Yui et al., 2002a). Although long-term MA abuse can lead to persistent psychotic symptoms, MA can also trigger psychotic symptoms in people vulnerable to psychosis. Lifetime MA abuse by individuals with a psychotic disorder ranges from 21% to 33% (Bu¨hler et al., 2002; Fowler et al., 1998; Mueser et al., 1990b; Pacific Community Resources, 2002), and drug abuse, particularly stimulant abuse, is associated with an earlier age at first hospitalization for schizophrenia (Bu¨hler et al., 2002; Hambrecht and Ha¨fner, 1996; Mueser et al., 1990a); more severe symptoms; and more problems in interpersonal relationships, motivation, role functioning, and activities (Addington and Addington, 1998). Although transient psychotic symptoms induced by MA may have distinguishing features such as paranoia, panic, hyperactivity, vivid auditory hallucinations, and obsessive-compulsive behaviors, persistent psychotic symptoms after MA abuse tend to be undistinguishable from those found in schizophrenia (Srisurapanont et al., 2011). Furthermore, Mikami et al. (2003) describe identical eyemovement dysfunction in individuals with persistent psychotic symptoms after MA abuse and in individuals with schizophrenia. Widespread MA use in North America is a fairly recent phenomenon, and therefore, little is known about the profiles of individuals whose MA-induced psychotic symptoms persist compared with those who experience temporary psychotic symptoms. Several risk factors are associated with the development of more severe or sustained psychosis after MA ingestion. Injection MA use increases the risk for developing more persistent psychotic symptoms compared with other routes of administration, such as inhalation and swallowing (Yui et al., 2002a, 2002b), as does binge use (e.g., daily use of MA for several days), compared with low dose daily or occasional use (Chen et al., 2003). Polysubstance abuse may also be associated with an increased risk for persistent psychotic disorders (Bretch et al., 2004; Halkitis, 2009). Other less investigated possible predictors of persistent psychosis in MA abusers have been suggested, including familial history of psychosis (Chen et al., 2005), antisocial personality traits, more severe depressive symptoms, and alcohol dependence (Chen et al., 2003). In mice, an enriched environment can protect from some of the negative effects of MA by preventing neurotoxicity and decreasing responsiveness to the drug (Bezard et al., 2003), suggesting that a negative environment, such as childhood trauma, could increase the risk for experiencing negative consequences from using MA, such as persistent psychotic symptoms. Trauma history is a risk factor for both substance abuse and schizophrenia (Cutajar et al., 2010), although it is not clear whether trauma exposure is related to the development of persistent psychotic symptoms after MA use.
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More research is needed to identify which individuals who experience psychotic symptoms after MA use have persistent symptoms to inform treatment of both their addiction and psychosis (Drake et al., 1998, 2004; Mueser et al., 2003). Other than a few case reviews suggesting the efficacy of electroconvulsive therapy (Grelotti et al., 2010) or of antipsychotic medication (Dore and Sweeting, 2006) for treating psychosis in MA users, the MA treatments investigated in North America so far have used an ‘‘addiction’’ treatment model for stimulant dependence that has not addressed comorbid mental health problems such as persistent psychotic symptoms (Cretzmeyer et al., 2003; Rawson et al., 2002; Reiber et al., 2000). To offer services that target the specific needs of individuals with persistent psychotic symptoms, a more thorough understanding of symptomatic profiles and of specific risk factors is warranted (Barr et al., 2006). The objective of this study was to identify the predictors of sustained psychotic symptoms after initial treatment of MA-related psychotic symptoms during the course of a 6-month follow-up period. The predictors included sociodemographic characteristics, patterns of MA use and other substance use, family history of psychosis, trauma history, antisocial personality traits, and depressive symptoms. On the basis of the extant literature, we hypothesized that persistent psychotic symptoms would be associated with a) more severe abuse of MA and other substances, b) family history of psychosis, c) more trauma exposure, d) antisocial personality disorder (ASPD) traits, and e) more severe depression.
METHODS This was a longitudinal study with a comprehensive battery of tests administered at baseline and 6-month follow-up and specific substance abuse and clinical measures administered monthly for 6 months. Demographic characteristics, family history of psychosis, history of substance abuse, trauma exposure, and antisocial personality traits were evaluated only at baseline. This study took place in Vancouver, British Columbia, from November 2005 until April 2011.
Participants A total of 295 participants were recruited. The inclusion criteria for this study were 18 years or older; MA use disorderVas defined by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition; presence of psychotic symptoms (four or more on hallucinations and/or unusual thought content on the Brief Psychiatric Rating ScaleYExpanded [BPRS-E; Ventura et al., 1993] within the last 2 weeks after MA ingestion); and less than 2 years since the initial diagnosis of MA-induced psychosis. The only exclusion criterion was inability to communicate in English. Two approaches to recruitment were used. First, 121 participants were approached after being admitted to the psychiatric emergency department of a collaborating hospital (Vancouver General Hospital, St. Paul’s Hospital, Children and Women’s Hospital, Riverview Hospital, or the Forensic Psychiatric Institute) because of florid psychotic symptoms. Second, 174 participants were recruited by a psychiatrist (W. M) who provided services in shelters, special housing for homeless individuals, or community organizations serving individuals with substance use problems (e.g., the Portland Hotel Society, Princess Rooms, Dodson and Jubilee Rooms, Dr. Peter Centre, and Directions). All necessary ethical approvals were obtained, and informed consent was carefully observed. Informed consent was determined by administering a 10-item true-false questionnaire about this study to the participants; those who did not obtain a perfect score after three trials were not allowed to participate (everyone succeeded). 1086
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Measures The participants completed two interviews for the baseline assessment and one for each monthly assessment and received a small stipend for their time. A self-report questionnaire was used to obtain information about age, sex, education, housing, concerns about illness, past diagnoses, and reasons for using MA. Substance use was assessed with the brief Addiction Severity Index (ASI; Zanis et al., 1997) and the Time-Line Follow-Back (TLFB; Sobell et al., 1980). The brief ASI assesses frequencies and quantities of psychoactive substances used, as well as impact (e.g., overdose). The TLFB elicits a specific week-by-week recollection of alcohol and drug use during the past month. Four measures of MA use were computed for each monthly assessment, including number of days used, number of grams ingested, method of ingestion (injected or other), and presence/absence of binging (93 days in a week using more than 1 g of MA). These four scores across all 6 months were summed to form total scores. For polysubstance abuse, a monthly score consisting of the number of different drugs used was calculated. Family history of psychosis was assessed using the screening questions from the Family Interview for Genetic Studies (Tsuang, 1994), which includes 15 questions (yes/no or don’t know) regarding the presence of family members who had behaviors, symptoms, or a diagnosis of a mental illness. The BPRS-E (Ventura et al., 1993) was used to determine psychosis at entry into this study and at every monthly time point. The 24-item semistructured interview was conducted by trained interviewers, following the guidelines from the University of California at Los Angeles. Depression was assessed monthly with the Beck Depression InventoryYII (Beck et al., 1996), which has 21 items and for which a score greater than 13 is considered clinically significant for mild depression; greater than 20, for moderate depression; and greater than 28, for severe depression (Beck et al., 1996). The mean score during the course of the 6 months of this study was used here. The Brief Trauma Questionnaire (BTQ; Schnurr et al., 1999) was administered to assess trauma exposure. The BTQ contains 10 simple yes/no questions, 3 of which assess childhood trauma, and has been extensively validated, including individuals with co-occurring disorders (Mueser et al., 2001). The Antisocial Personality Disorder Scale was used at baseline, which is a structured interview based on the Structured Clinical Interview for DSM-IV, Axis II (First et al., 1997), used to ascertain ASPD traits and diagnosis and including childhood conduct disorder.
Analyses Trajectory analyses were used to identify significantly distinct subgroups of participants on the basis of the pattern of their psychotic symptoms during the 6-month period. The psychotic symptom score used at each time point was the six-item BPRS positive symptom scale. The trajectory analyses were conducted using the SAS Proc Traj procedure developed by Jones et al. (2001). The procedure uses mixture models for estimating developmental trajectories, enabling one to identify the number and the polynomial form of different trajectories present in a sample, as well as offering the probability of each subject belonging to an identified trajectory. The end solution regarding the number and the form of trajectories is the one that minimizes the Akaike’s information criteria. Following this, each subject is assigned to the most probable trajectory. Similar to cluster analysis, the trajectory analysis groups individuals rather than variables. The SAS Proc Traj procedure assumes that data are missing at random and therefore includes all the subjects in the analyses. To identify potential predictors of persistent psychosis, the trajectories were then compared with the Pearson’s chi-square tests for categorical variables and with the Student’s t-tests for continuous variables. The significant variables were then entered into a logistic regression, using Forward Wald, to * 2013 Lippincott Williams & Wilkins
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FIGURE 1. Individuals’ trajectories during this study on the BPRS positive symptoms.
determine which predictors most uniquely predicted the persistent psychosis trajectory.
RESULTS Of the 295 participants assessed at baseline, 223 were included in the trajectory analysis because they had completed assessments for at least two time points, excluding the baseline. Given that one of the inclusion criteria for this study was high psychotic symptoms, we did not include the baseline BPRS score for positive symptoms in the analysis. Of the 295 initially included in this study, 158 could be contacted for the 6-month assessment. Those who did not complete the last assessment were significantly younger (t[201] = 2.66, p G 0.05; mean, 30.9; SD, 11.1 vs. mean, 35.5; SD, 10.3), had more
severe psychiatric symptoms (but not specifically psychotic symptoms; t[221] = 2.34, p G 0.05), used smaller quantities of MA at baseline (t[173] = 1.79, p G 0.05), and were less likely to inject MA (t[221] = 2.2, p G 0.05). The trajectory analyses generated two groupsVone with lower psychotic symptoms (70.2%, n = 157) and one with more persistent psychotic symptoms (29.8%, n = 66; see Figure 1; see Table 1 for demographic and clinical characteristics of each trajectory group). Comparisons of the two groups on baseline characteristics indicated that those with persistent psychotic symptoms were significantly older (see Table 1), had higher baseline psychotic symptoms (t[221] = 1.57, p G 0.001), had higher baseline depressive symptoms (t[221] = 4.09, p G 0.001), and had higher baseline overall
TABLE 1. Sociodemographic and Clinical Characteristics of the Low Psychosis and Persistent Psychosis Trajectory Groups Low/Persistent Psychosis Variables (n)/Category
Sex (n = 223)/male Age (n = 203) Education (n = 203) Birth country (n = 223)/Canada Family history of psychosis (n = 183) No. years of MA use (n = 222) No. years of regular alcohol use (n = 222) No. years of cannabis use (n = 222) Total no. days of MA use (n = 191) Total no. grams of MA useda (n = 191) MA injection scoreb (n = 221) No. substances used (n = 219) Binge scorec (n = 219) ASPD traits (n = 217) Met the criteria for ASPD Childhood trauma score (n = 220) Total trauma exposure Total BDI score (n = 221) Total BPRS total score (n = 221)
Mean (SD) or n (%)
111 (73%) 32.90 (10.83) 10.64 (2.30) 141 (89%) 52 (38.8%) 4.11 (5.29) 6.12 (7.41) 10.47 (9.68) 50.09 (51.31) 4.96 (6.87) 5.49 (8.09) 4.72 (2.09) 1.98 (1.81) 20.96 (3.79) 81 (54%) 1.36 (1.27) 8.96 (4.79) 11.20 (7.69) 36.07 (12.99)
46 (69%) 38.11 (9.60) 10.80 (2.53) 60 (94%) 23 (46.9%) 6.58 (8.00) 9.29 (11.44) 13.46 (12.34) 49.02 (47.16) 4.10 (4.62) 4.94 (7.00) 4.98 (2.21) 1.75 (1.79) 22.13 (4.29) 44 (69%) 1.26 (1.34) 9.05 (4.87) 15.66 (9.18) 46.88 (19.47)
Statistical Test
Significance
W = 2.41 t = j3.14 t = j0.41 W2 = 10.33 W2 = 1.85 t = j2.29 t = j2.07 t = j1.75 t = 0.14 t = 0.14 t = 0.48 t = j0.06 t = 0.87 t = j1.98 W2 = 5.04 t = 0.48 t = j0.12 t = j3.43 t = j4.09
p = 0.30 p = 0.002* p = 0.69 p = 0.67 p = 0.76 p = 0.02* p = 0.04* p = 0.08 p = 0.89 p = 0.89 p = 0.63 p = 0.95 p = 0.38 p = 0.05* p = 0.08 p = 0.64 p = 0.91 p = 0.001** p = 0.000**
2
a
Range, 0.03 to 38 g. Score calculated in number of weeks MA was injected during the study. For each month of this study, a score of 1 was given if a person used more than 1 g of MA during a binge (minimum of 3 days in a row). *p G .05. **p G .001. b c
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symptoms (t[221] = 7.77, p G 0.001). No differences were found in terms of baseline negative symptoms (p = 0.42). The persistent psychosis trajectory group had been using MA and alcohol for significantly more years. There were significantly more individuals in the persistent psychosis group with ASPD traits, although only a trend in terms of an ASPD diagnosis. No significant differences were found for family history of psychosis or childhood trauma. In terms of continuous measures taken during this study, those who were more depressed across the time points were also more likely to be in the persistent psychosis trajectory group. No significant differences were found between the groups on any of the measures of MA use during the 6-month study period (days, grams, injection, and binging) or for polysubstance abuse. Among the baseline variables, logistic regression indicated that the most significant predictors of persistent psychotic symptoms were having high baseline psychotic symptoms (odds ratio, 12.04; 95% confidence interval [CI], 3.53Y12.04) and having used MA for more years (odds ratio, 1.18; 95% CI, 0.99Y1.18). As for the continuous variables collected during this study, high depression scores on the BDI during the course of 6 months was the sole predictor of being in the persistent psychosis group (odds ratio, 3.43; 95% CI, 1.74Y6.76, p G 0.001).
DISCUSSION The purpose of this study was to determine the profiles of individuals with more sustained psychotic symptoms after MA abuse. We found a slightly higher proportion of MA users whose psychotic symptoms persisted over time than those in the study of Yui et al. (2002b), 30% vs. 21%, respectively. Two factors that may have contributed to the higher percentage of people with persistent psychosis in this sample were that all users were living in the community and not abstinent of drugs or incarcerated, in contrast to the study of Yui et al. (2002b), and the users had longer exposure to MA (6 years vs. 8 months, respectively), suggesting that longer use of MA is associated with persistent psychosis. Contrary to the study of Chen et al. (2005), we did not find an association between family history of psychosis and persistent psychosis, although 23% of our sample reported having a family member with psychosis. Rather, the individuals who experienced persistent psychosis were older and long-time MA users with more severe initial psychotic symptoms and depression than those with transient psychosis. Similar findings have been reported elsewhere with an abstinent sample (Lichlyter et al., 2011). Although family history of psychosis was not predictive of persistent psychosis after MA use, direct family interviews were not conducted, and thus, our results do not rule out increased vulnerability to schizophrenia as a contributing factor, as suggested by Mikami et al. (2003). Given that more years of MA abuse were linked to higher likelihood of having sustained psychotic symptoms, the findings somewhat support the neurotoxicity model whereby long-term MA abuse can alter the dopamine system, resulting in more severe and more persistent psychotic symptoms similar to those found in untreated schizophrenia (Barr et al., 2006). In our study, severity of depression during the 6-month follow-up period was the second strongest predictor of sustained psychotic symptoms, after initial psychosis severity. Depression is common in individuals with MA dependence without psychosis, with rates varying from 13% (Salo et al., 2011) to as high as 64% (Conway et al., 2006). In the MA users with concurrent psychotic symptoms in this sample, the rates were even higher, with 67% scoring as clinically depressed at baseline (Lecomte et al., 2010). Extensive research documents that psychosis and depression are strongly linked, with depression being a consistent syndrome across the long-term course of schizophrenia (Ha¨fner et al., 2008). Furthermore, individuals with major depression have even more severe depression when psychotic symptoms are also present (Gaudiano et al., 2009). 1088
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The finding that individuals with persistent psychosis had more antisocial behavior traits might be linked to the fact that more severe substance abuse is associated with antisocial traits, which, in turn, could lead to more damaging consequences on mental health and quality of life (Mueser et al., 2006). It could also be explained by early social isolation caused by disruptive childhood conduct behaviors, leading to a poorer social network that is unlikely to help when someone starts becoming psychotic. This result reflects the sample of individuals seeking psychiatric help in our studyVmost were polysubstance users, living in the margin of society as indicated by low employment and unstable housing (Lecomte et al., 2010)V and for whom many ‘‘antisocial’’ behaviors are considered survival behaviors on the streets. Polysubstance abuse and childhood abuse were not more prevalent in either psychosis subgroup but were highly prevalent in the sample as a whole (96% and 56%, respectively), also reflecting the important comorbidities found in our sample. We were unable to specifically look at childhood sexual abuse, increasingly reported as being linked to psychosis (Bendall et al., 2008), given that the trauma measure used (BTQ) has questions on sexual assault but not according to age. We were also intrigued by the mean age of our sample, which was older than what we had anticipated. In fact, it seems that MA appeals not only to young individuals but also to more experienced drug users, given the low cost and the rapid intoxicating effects. One limitation of this study was the significant attrition of the participants at the 6-month follow-up, with only 54% of the sample available for assessment, although 76% of the sample was evaluated for at least two follow-up assessments. Contrary to many other studies that focused on single-drug users and excluded individuals with previous psychiatric diagnoses, our sample was more ecologically representative of the individuals who abuse MA and who seek psychiatric help for psychotic symptoms. As such, we cannot infer that the psychotic symptoms were linked to only MA abuse, and a primary psychosis may have been present in some users, although MA was considered the drug of choice for most of our sample (Lecomte et al., 2010). This study found that among treatment-seeking MA users with psychotic symptoms, persistent psychosis was associated with older age, more years of MA and alcohol abuse, and presentation of more severe psychotic and depressive symptoms. More work is needed to develop treatment programs that target the special needs of people with co-occurring MA addiction and psychosis. The present study takes a step toward accomplishing this by identifying individuals with MA-induced psychosis whose psychotic symptoms are likely to persist and who are most likely to benefit from comprehensive treatment designed to integrate the management of the psychiatric symptoms with treatment of the addiction. ACKNOWLEDGMENTS The authors thank the participants from Vancouver, Burnaby, and South Fraser who took part in this project as well as the research assistants, the clinicians, and the MARC members who helped along the way. DISCLOSURES This research was supported by two Canadian Institute of Health Research (CIHR) grants as well as by the Provincial Health Services Authorities of British Columbia. The first author was a CIHR and Michael Smith Foundation award recipient during this study. The authors declare no conflict of interest. REFERENCES Addington J, Addington D (1998) Effect of substance misuse in early psychosis. Br J Psychiatry Suppl. 172:134Y136.
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