Bipolar Disorder and Substance Abuse -- Neurotransmitter.net

(Updated 1/12/04)

Cassidy F, Ahearn EP, Carroll BJ.
Substance abuse in bipolar disorder.
Bipolar Disord 2001 Aug;3(4):181-8
"BACKGROUND: High rates of substance abuse have been reported in the general population, with males more often affected than females. Although high rates of substance abuse have also been reported in bipolar patients, the relationship between substance abuse and bipolar disorder has not been well characterized. METHODS: Substance abuse histories were obtained in 392 patients hospitalized for manic or mixed episodes of bipolar disorder and rates of current and lifetime abuse calculated. Analyses comparing sex, subtype (manic vs. mixed) and clinical history variables were conducted. RESULTS: Rates of lifetime substance abuse were high for both alcohol (48.5%) and drugs (43.9%). Nearly 60% of the cohort had a history of some lifetime substance abuse. Males had higher rates of abuse than females, but no differences in substance abuse were observed between subjects in manic and mixed bipolar states. Rates of active substance abuse were lower in older age cohorts. Subjects with a comorbid diagnosis of lifetime substance abuse had more psychiatric hospitalizations. CONCLUSIONS: Substance abuse is a major comorbidity in bipolar patients. Although rates decrease in older age groups, substance abuse is still present at clinically important rates in the elderly. Bipolar patients with comorbid substance abuse may have a more severe course. These data underscore the significance of recognition and treatment of substance abuse in bipolar disorder patients." [Abstract]

Goodwin RD, Stayner DA, Chinman MJ, Wu P, Tebes JK, Davidson L.
The relationship between anxiety and substance use disorders among individuals with severe affective disorders.
Compr Psychiatry. 2002 Jul-Aug;43(4):245-52.
"We sought to determine the association between anxiety disorders and substance use disorders among patients with severe affective disorders in a community-based outpatient treatment program. Two hundred sixty participants in a supported socialization program were assessed using the Structured Clinical Interview for DSM-III-R (SCID). Multivariate logistic regression analyses were used to determine the relationship between anxiety disorders and alcohol and substance use disorders among patients with severe and persistent affective disorders (i.e., major depression and bipolar disorder). Among patients with severe and persistent affective disorders, cocaine (odds ratio [OR] = 5.9 [1.4, 24.6]), stimulant (OR = 5.1 [1.2, 20.9]), sedative (OR = 5.4 [1.2, 24.7]), and opioid use disorders (OR = 13.9 [1.4, 138.7]) were significantly more common among those with, compared with those without, anxiety disorders. This association persisted after adjusting for differences in sociodemographic characteristics and comorbid psychotic disorders. Significant associations between panic attacks, social phobia, specific phobia, and obsessive-compulsive disorder (OCD) and specific substance use disorders were also evident. These findings are consistent with and extend previous results by documenting an association between anxiety disorders and substance use disorders, independent of comorbid psychotic disorders among patients in a outpatient psychiatric rehabilitation program. These data highlight the prevalence of comorbid anxiety disorders, a potentially undetected and therefore undertreated problem, among patients with severe affective disorders and substance use comorbidity. Future work is needed to determine the nature of this association and to determine whether treatment of one prevents onset of the other." [Abstract]

Skinstad AH, Swain A.
Comorbidity in a clinical sample of substance abusers.
Am J Drug Alcohol Abuse 2001 Feb;27(1):45-64
"The sample consisted of 125 male inpatients admitted to one of two substance abuse treatment centers in Iowa. They were diagnosed by means of the Diagnostic Interview Schedule Screening Interview-Quick-DIS version, the Structural Interview for DSM-III-R Personality Disorder (PD), revised, and the Substance Abuse Reporting System. The most frequently diagnosed comorbid Axis I conditions were anxiety and mood disorders, while the most frequently observed Axis II disorders were in Cluster B, borderline PD, and antisocial PD followed by Cluster C, avoidant PD, passive-aggressive PD and obsessive-compulsive PD; and then Cluster A; schizoid PD. Subjects diagnosed with Borderline PD showed the highest rate of comorbid psychopathology, including Axis I disorders of generalized anxiety disorder, major depression, cocaine dependence, and inhalant dependence. The most likely comorbid diagnosis for antisocial PD subjects was bipolar disorder. The schizoid PD and the NoPD groups were less likely to meet criteria for other Axis I disorders. A high rate of comorbid Axis II pathology was also found. Polysubstance dependent subjects were more likely to be diagnosed with anxiety disorder or bipolar disorder than were those who were not polysubstance dependent or were dependent only on alcohol. Polysubstance dependent men were at highest risk for Axis II disorders: 56% of them met criteria for a Cluster B PD, with borderline PD and histrionic PD most frequent." [Abstract]

Shrier LA, Harris SK, Kurland M, Knight JR.
Substance use problems and associated psychiatric symptoms among adolescents in primary care.
Pediatrics. 2003 Jun;111(6 Pt 1):e699-705.
"OBJECTIVE: Substance use disorders (SUDs) are associated with other mental disorders in adolescence, but it is unclear whether less severe substance use problems (SUPs) also increase risk. Because youths with SUPs are most likely to present first to their site of primary care, it is important to establish the presence and patterns of psychiatric comorbidity among adolescent primary care patients with subdiagnostic use of alcohol or other drugs. The objective of this study was to determine the association between level of substance use and psychiatric symptoms among adolescents in a primary care setting. METHODS: Patients who were aged 14 to 18 years and receiving routine care at a hospital-based adolescent clinic were eligible. Participants completed the Problem Oriented Screening Instrument for Teenagers Substance Use/Abuse scale, which is designed to detect social and legal problems associated with alcohol and other drugs, and the Adolescent Diagnostic Interview, which evaluates for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnoses of substance abuse/dependence and 8 types of psychiatric symptoms. We examined gender-specific associations of no/nonproblematic substance use (NSU), SUP, and SUD with psychiatric symptom presence (any symptoms within each type), score (symptom scores summed across all types), and number of types (number of different symptom types endorsed). RESULTS: Of 538 adolescents (68% female; mean +/- standard deviation age: 16.6 +/- 1.4 years), 66% were classified with NSU, 18% with SUP, and 16% with SUD, and 80% reported having at least 1 type of psychiatric symptom in the previous 12 months. Symptoms of anxiety were most common (60% of both boys and girls), followed by symptoms of depression among girls (51%) and symptoms of attention-deficit disorder (ADD) among boys (47%). Compared with those with NSU, youths with SUP and those with SUD were more likely to report symptom presence for several types of psychiatric symptoms. Girls with SUP or SUD had increased odds of reporting symptoms of mania, ADD, and conduct disorder; girls with SUD were at increased risk for symptoms of depression, eating disorders, and hallucinations or delusions. Boys with SUP had increased odds of ADD symptoms, whereas boys with SUD had increased odds of reporting hallucinations or delusions. Boys with SUP or SUD had increased odds of reporting symptoms of conduct disorder. Youths with SUP and SUD also had higher psychiatric symptom scores and reported a wider range of psychiatric symptom types (number of types) compared with youths with NSU. CONCLUSIONS: Like those with SUD, adolescents with subdiagnostic SUP were at increased risk for experiencing a greater number of psychiatric symptoms and a wider range of psychiatric symptom types than youths with NSU. Specifically, adolescents with SUP are at increased risk for symptoms of mood (girls) and disruptive behavior disorders (girls and boys). These findings suggest the clinical importance of SUP and support the concept of a continuum between subthreshold and diagnostic substance use among adolescents in primary care. Identification of youths with SUP may allow for intervention before either the substance use or any associated psychiatric problems progress to more severe levels." [Abstract]

Wilens TE, Biederman J, Millstein RB, Wozniak J, Hahesy AL, Spencer TJ.
Risk for substance use disorders in youths with child- and adolescent-onset bipolar disorder.
J Am Acad Child Adolesc Psychiatry 1999 Jun;38(6):680-5
"OBJECTIVE: Previous work in adults has suggested that early-onset bipolar disorder (BPD) is associated with an elevated risk for substance use disorders (SUD). To this end, the authors assessed the risk for SUD in child- versus adolescent-onset BPD with attention to comorbid psychopathology. METHOD: All youths (aged 13-18 years) with available structured psychiatric interviews were studied systematically. From clinic subjects (N = 333), 86 subjects with DSM-III-R BPD were identified. To evaluate the risk for SUD and BPD while attending to developmental issues, the authors stratified the BPD sample into those with child-onset BPD (< or = 12 years of age, n = 50) and those with adolescent-onset BPD (13-18 years of age, n = 36). RESULTS: In mid-adolescence, youths with adolescent-onset BPD were at significantly increased risk for SUD relative to those with child-onset BPD (39% versus 8%; p = .001). Compared with those with child-onset BPD, those with adolescent-onset BPD had 8.8 times the risk for SUD (95% confidence interval = 2.2-34.7; chi 7(2) = 9.7, p = .002). The presence of conduct disorder or other comorbid psychopathology within BPD did not account for the risk for SUD. CONCLUSIONS: Adolescent-onset BPD is associated with a much higher risk for SUD than child-onset BPD, which was not accounted for by conduct disorder or other comorbid psychopathology. Youths with adolescent-onset BPD should be monitored and educated about SUD risk. The identification and treatment of manic symptomatology may offer therapeutic opportunities to decrease the risk for SUD in these high-risk youths." [Abstract]

Biederman J, Faraone SV, Wozniak J, Monuteaux MC.
Parsing the association between bipolar, conduct, and substance use disorders: a familial risk analysis.
Biol Psychiatry 2000 Dec 1;48(11):1037-44
"BACKGROUND: Bipolar disorder has emerged as a risk factor for substance use disorders (alcohol or drug abuse or dependence) in youth; however, the association between bipolar disorder and substance use disorders is complicated by comorbidity with conduct disorder. We used familial risk analysis to disentangle the association between the three disorders. METHODS: We compared relatives of four proband groups: 1) conduct disorder + bipolar disorder, 2) bipolar disorder without conduct disorder, 3) conduct disorder without bipolar disorder, and 4) control subjects without bipolar disorder or conduct disorder. All subjects were evaluated with structured diagnostic interviews. For the analysis of substance use disorders, Cox proportional hazard survival models were utilized to compare age-at-onset distributions. RESULTS: Bipolar disorder in probands was a risk factor for both drug and alcohol addiction in relatives, independent of conduct disorder in probands, which was a risk factor for alcohol dependence in relatives independent of bipolar disorder in probands, but not for drug dependence. The effects of bipolar disorder and conduct disorder in probands combined additively to predict the risk for substance use disorders in relatives. CONCLUSIONS: The combination of conduct disorder + bipolar disorder in youth predicts especially high rates of substance use disorders in relatives. These findings support previous results documenting that when bipolar disorder and conduct disorder occur comorbidly, both are validly diagnosed disorders." [Abstract]

Frye MA, Altshuler LL, McElroy SL, Suppes T, Keck PE, Denicoff K, Nolen WA, Kupka R, Leverich GS, Pollio C, Grunze H, Walden J, Post RM.
Gender differences in prevalence, risk, and clinical correlates of alcoholism comorbidity in bipolar disorder.
Am J Psychiatry. 2003 May;160(5):883-9.
"OBJECTIVE: The prevalence of lifetime alcohol abuse and/or dependence (alcoholism) in patients with bipolar disorder has been reported to be higher than in all other axis I psychiatric diagnoses. This study examined gender-specific relationships between alcoholism and bipolar illness, which have previously received little systematic study. METHOD: The prevalence of lifetime alcoholism in 267 outpatients enrolled in the Stanley Foundation Bipolar Network was evaluated by using the Structured Clinical Interview for DSM-IV. Alcoholism and its relationship to retrospectively assessed measures of the course of bipolar illness were evaluated by patient-rated and clinician-administered questionnaires. RESULTS: As in the general population, more men (49%, 57 of 116) than women with bipolar disorder (29%, 44 of 151) met the criteria for lifetime alcoholism. However, the risk of having alcoholism was greater for women with bipolar disorder (odds ratio=7.35) than for men with bipolar disorder (odds ratio=2.77), compared with the general population. Alcoholism was associated with a history of polysubstance use in women with bipolar disorder and with a family history of alcoholism in men with bipolar disorder. CONCLUSIONS: This study suggests that there are gender differences in the prevalence, risk, and clinical correlates of alcoholism in bipolar illness. Although this study is limited by the retrospective assessment of illness variables, the magnitude of these gender-specific differences is substantial and warrants further prospective study." [Abstract]

Sloan KL, Kivlahan D, Saxon AJ.
Detecting bipolar disorder among treatment-seeking substance abusers.
Am J Drug Alcohol Abuse 2000 Feb;26(1):13-23
"Bipolar disorder is increasingly recognized to have frequent comorbidity with substance use disorders, but may be difficult to diagnose among patients with active substance use. The purpose of this paper is to describe a brief, self-report form for the efficient detection of bipolar disorder. The 19-item form was piloted in 373 consecutive applicants for substance abuse treatment at an urban Veterans Affairs (VA) medical center. Results show reasonable internal consistency (alpha = .850) and high rates of manic symptomatology (36%), previous bipolar diagnosis (30%, 51% of whom report prior psychiatric hospitalization), and exposure to mood stabilizers (20%, 66% of whom reported therapeutic benefit). Comparison of nine different scoring algorithms with chart diagnosis as the validating criterion found that self-report of bipolar diagnosis was optimally sensitive. Either self-report of bipolar diagnosis with hospitalization or self-report of exposure to mood stabilizers with therapeutic response was optimally specific. Symptom self-report items had significantly poorer sensitivity and specificity (F = 7.60, p < .01). We conclude that questions pertaining to diagnostic and treatment history (especially hospitalization or therapeutic medication response) are considerably superior to symptom-based screening for clinically diagnosed bipolar disorder. Further work using structured interview as the diagnostic criterion is under way to validate this instrument." [Abstract]

Chengappa KN, Levine J, Gershon S, Kupfer DJ.
Lifetime prevalence of substance or alcohol abuse and dependence among subjects with bipolar I and II disorders in a voluntary registry.
Bipolar Disord 2000 Sep;2(3 Pt 1):191-5
"OBJECTIVE: To evaluate the prevalence of substance abuse dependence and/or alcohol abuse dependence among subjects with bipolar I versus bipolar II disorder in a voluntary registry. METHOD: One hundred randomly selected registrants in a voluntary case registry for bipolar disorder were interviewed, using the Structured Clinical Interview for DSM-IV Axis I Disorders, to validate the diagnosis of this registry. Corroborative information was obtained from medical records, family members and the treating psychiatrist. Eighty-nine adults (18-65 years) met criteria for bipolar disorder (bipolar I = 71, bipolar II = 18) and were included in this analysis. RESULTS: Forty-one (57.8%) subjects with bipolar I disorder abused, or were dependent on one or more substances or alcohol, 28.2% abused, or were dependent on, two substances or alcohol, and 11.3% abused or were dependent on three or more substances or alcohol. Nearly 39% of bipolar II subjects abused or were dependent on one or more substances, nearly 17% were dependent on two or more substances or alcohol, and 11% were dependent on three or more substances or alcohol. Alcohol was the most commonly abused drug among either bipolar I or II subjects. CONCLUSIONS: Consistent with other epidemiologic and hospital population studies, this voluntary bipolar disorder registry suggests a high prevalence of comorbidity with alcohol and/or substance abuse dependence. Bipolar I subjects appear to have higher rates of these comorbid conditions than bipolar II subjects; however, as the number of bipolar II subjects was rather small, this suggestion needs confirmation." [Abstract]
Escamilla MA, Batki S, Reus VI, Spesny M, Molina J, Service S, Vinogradov S, Neylan T, Mathews C, Meza L, Gallegos A, Montero AP, Cruz ML, Neuhaus J, Roche E, Smith L, Leon P, Freimer NB.
Comorbidity of bipolar disorder and substance abuse in Costa Rica: pedigree- and population-based studies.
J Affect Disord. 2002 Sep;71(1-3):71-83.
"BACKGROUND: The purpose of this study was to determine the prevalence of substance use disorders (substance abuse or substance dependence: SA/SD) in a large sample of Bipolar Type I (BPI) patients drawn from the Costa Rican population and to describe the effects of SA/SD on the course of their bipolar disorder. METHOD: 110 subjects from two high-risk (for BPI) Costa Rican pedigrees and 205 unrelated Costa Rican BPI subjects were assessed using structured interviews and a best estimate process. Chi(2) and survival analyses were performed to assess the effect of gender on comorbidity risk, and the effect of comorbidity on the clinical course of BPI. RESULTS: SA/SD (primarily alcohol dependence) occurred in 17% of the BPI patients from the population sample and 35% of the BPI patients from the pedigree sample. Comorbid SA/SD was strongly associated with gender chi(2) = 16.84, P = 0.00004). In comorbid subjects, alcohol dependence tended to predate the first manic episode (chi(2) = 6.54, P < 0.025). History of SA/SD did not significantly alter the prevalence of psychosis or age of onset of mania in BPI subjects. CONCLUSIONS: These results suggest that SA/SD comorbidity rates are lower in this type of population than in BPI patient populations in the US. Gender is a strong predictor of comorbidity prevalence in BPI patients from this population. Although SA/SD may be a risk factor for precipitating BPI in those at risk, in this population comorbid BPI subjects do not have a different onset or course of BPI in comparison to BPI patients without comorbidity." [Abstract]
Salloum IM, Thase ME.
Impact of substance abuse on the course and treatment of bipolar disorder.
Bipolar Disord 2000 Sep;2(3 Pt 2):269-80
"OBJECTIVES: The objectives of this article are to review the prevalence, natural history, pathophysiology, and treatment of comorbid bipolar disorder with alcoholism and other psychoactive substance use disorders (PSUDs). METHODS: All identified bibliographies through a literature search of all Medline files and bibliographies of selected articles focusing on the prevalence, natural history, course, prognosis, inter-relationship, and treatment of bipolar disorder with comorbid alcoholism and other PSUDs were reviewed. RESULTS AND CONCLUSIONS: Comorbidity of bipolar disorder and alcoholism and other PSUDs is highly prevalent. The presence of this so called 'dual diagnoses' creates a serious challenge in terms of establishing an accurate diagnosis and providing appropriate treatment interventions. The inter-relationship between these disorders appears to be mutually detrimental. The course, manifestation, and treatment of each condition are significantly compounded by the presence of the other condition. Substance abuse and alcoholism appear to significantly complicate the course and prognosis of bipolar disorder resulting in increased suffering, disability, and costs. On the other hand, bipolar disorder may be a risk factor for developing PSUDs. Although, there are a number of hypotheses explaining the pathophysiological mechanism involved in such comorbidities, our understanding of the exact nature of such neurobiological mechanisms is still limited. While the antikindling agents and targeted psychotherapeutic techniques may be useful intervention strategies, there is still a significant lack of empirically based treatment options for these patients." [Abstract]
Sutor B, Tinsley JA, Morse RM.
Management of patients with bipolar mood disorder and substance dependence.
J Addict Dis 1999;18(1):83-93
"Nine patients with bipolar mood disorder and concurrent substance dependence were treated in an 18-bed inpatient addiction unit over a 3-month period. A multidisciplinary team approach used a medicalized Minnesota model and stressed the establishment of a positive diagnosis and individualization of management strategies for each patient. Clinically significant affective symptoms that required acute psychiatric intervention developed in several patients during hospitalization. Manic symptoms developed in three patients during sedative withdrawal, requiring the team to differentiate manic symptoms from physiologic withdrawal; and two patients became severely depressed, requiring pharmacologic management and suicide-prevention strategies. SUMMARY: Our experience with the patients in this case series supports the contention that there is no simple, uniform approach to the substance-dependent patient with bipolar disorder. Treatment teams must be prepared to differentiate complex syndromes and to manage manic, depressive, and addictive behaviors." [Abstract]
Potash JB, Kane HS, Chiu YF, Simpson SG, MacKinnon DF, McInnis MG, McMahon FJ, DePaulo JR Jr.
Attempted suicide and alcoholism in bipolar disorder: clinical and familial relationships.
Am J Psychiatry 2000 Dec;157(12):2048-50
"OBJECTIVE: This study examined the clinical and familial relationships between comorbid alcoholism and attempted suicide in affectively ill relatives of probands with bipolar I disorder. METHOD: In 71 families ascertained for a genetic linkage study, 337 subjects with major affective disorder were assessed by using the Schedule for Affective Disorders and Schizophrenia-Lifetime Version. RESULTS: Subjects with bipolar disorder and alcoholism had a 38.4% lifetime rate of attempted suicide, whereas those without alcoholism had a 21.7% rate. Attempted suicide among subjects with bipolar disorder and alcoholism clustered in a subset of seven families. Families with alcoholic and suicidal probands had a 40.7% rate of attempted suicide in first-degree relatives with bipolar disorder, whereas other families had a 19.0% rate. CONCLUSIONS: Comorbid alcoholism was associated with a higher rate of attempted suicide among family members with bipolar disorder. Attempted suicide and alcoholism clustered in a subset of families. These relationships may have a genetic origin and may be mediated by intoxication, mixed states, and/or temperamental instability." [Abstract]
Simon GE, Unutzer J.
Health care utilization and costs among patients treated for bipolar disorder in an insured population.
Psychiatr Serv 1999 Oct;50(10):1303-8
"OBJECTIVE: The study examined health care utilization and costs among patients treated for bipolar-spectrum disorders in an insured population. METHODS: Computerized data on prescriptions and on outpatient and inpatient diagnoses from a large health plan were used to identify patients treated for cyclothymia, bipolar disorder, or schizoaffective disorder. Three age- and sex-matched comparison groups consisting of general medical outpatients, patients treated for depression, and patients treated for diabetes were selected from health plan members. Utilization and cost of health services for the four groups over a six-month period were assessed using computerized accounting records. RESULTS: Total mean+/-SD costs for patients in the bipolar disorder group ($3,416+/-$6,862) were significantly higher than those in any of the comparison groups. Specialty mental health and substance abuse services accounted for 45 percent of total costs in the group with bipolar disorder (mean+/-SD=$1, 566+/-$3,243), compared with 10 percent in the group with depression. Among patients treated for bipolar disorder, 5 percent of patients accounted for approximately 40 percent of costs for specialty mental health and substance abuse services, 90 percent of inpatient costs for specialty mental health and substance abuse services, and 95 percent of out-of-pocket costs for inpatient care. In the bipolar disorder group, parity coverage of inpatient mental health and substance abuse services would increase overall health care costs by 6 percent. CONCLUSIONS: Health care costs for patients with bipolar disorder exceed those for patients treated for depression or diabetes, and specialty mental health and substance abuse treatment costs account for this difference. Costs to the insurer and costs borne by patients are accounted for by a small proportion of patients. Elimination of discriminatory mental health coverage would have a small effect on overall health care costs." [Abstract]
Carey KB, Carey MP, Simons JS.
Correlates of substance use disorder among psychiatric outpatients: focus on cognition, social role functioning, and psychiatric status.
J Nerv Ment Dis. 2003 May;191(5):300-8.
"This study compared psychiatric outpatients who were never, former, and current substance abusers on psychiatric, social, and cognitive functioning. Fifty-six outpatients with schizophrenia spectrum and bipolar disorders volunteered to complete diagnostic and social role function interviews, self-report inventories, and neuropsychological tests. Multinomial logit regression analyses indicated that current and former abusers reported greater subjective feelings of distress than those who never abused. Contrary to expectations, however, both groups of substance abusers performed better on nonverbal cognitive tests compared with those who never abused. Differences in social functioning were also observed: former abusers demonstrated better instrumental role functioning than those who never abused. This pattern of findings challenges assumptions about additive effects of comorbid disorders on cognitive and social functioning." [Abstract]
Preisig M, Fenton BT, Stevens DE, Merikangas KR.
Familial relationship between mood disorders and alcoholism.
Compr Psychiatry 2001 Mar-Apr;42(2):87-95
"Clinical and epidemiological studies have consistently revealed an association between alcohol use disorders and both bipolar and nonbipolar mood disorders. However, the evidence regarding the nature of these associations is unclear. The familial patterns of alcohol and affective disorders were examined using data from a controlled family study of probands with alcohol and anxiety disorders who were sampled from treatment settings and the community. The substantial degree of comorbidity between mood and anxiety disorders among probands allowed for the examination of comorbidity and familial aggregation of alcohol and mood disorders. The major findings are that (1) alcoholism was associated with bipolar and nonbipolar mood disorders in the relatives; (2) there was a strong degree of familial aggregation of alcohol dependence and both types of mood disorders were observed; and (3) there was no evidence of cross-aggregation (i.e., increase in mood disorders among probands with alcohol dependence, and vice versa) between alcoholism and mood disorders. The independent familial aggregation of bipolar disorder and alcoholism and the finding that the onset of bipolar disorder tended to precede that of alcoholism are compatible with a self-medication hypothesis as the explanation for the frequent co-occurrence of these disorders. In contrast, the independent familial aggregation and the tendency of an earlier onset of alcoholism than that of nonbipolar depression suggest that unipolar mood disorders are frequently secondary to alcoholism. Copyright 2001 by W.B. Saunders Company." [Abstract]
Tiihonen J, Hallikainen T, Lachman H, Saito T, Volavka J, Kauhanen J, Salonen JT, Ryynanen OP, Koulu M, Karvonen MK, Pohjalainen T, Syvalahti E, Hietala J.
Association between the functional variant of the catechol-O-methyltransferase (COMT) gene and type 1 alcoholism.
Mol Psychiatry 1999 May;4(3):286-9
"Catechol-O-methyltransferase (COMT) is an enzyme which has a crucial role in the metabolism of dopamine. It has been suggested that a common functional genetic polymorphism in the COMT gene, which results in 3 to 4-fold difference in COMT enzyme activity, may contribute to the etiology of mental disorders such as bipolar disorder and alcoholism. Since ethanol-induced euphoria is associated with the rapid release of dopamine in limbic areas, it is conceivable that subjects who inherit the allele encoding the low activity COMT variant would have a relatively low dopamine inactivation rate, and therefore would be more vulnerable to the development of ethanol dependence. The aim of this study was to test this hypothesis among type 1 (late-onset) alcoholics. The COMT polymorphism was determined in two independent male late onset (type 1) alcoholic populations in Turku (n = 67) and Kuopio (n = 56). The high (H) and low (L) activity COMT genotype and allele frequencies were compared with previously published data from 3140 Finnish blood donors (general population) and 267 race- and gender-matched controls. The frequency of low activity allele (L) was markedly higher among the patients both in Turku (P = 0.023) and in Kuopio (P = 0.005) when compared with the general population. When all patients were compared with the general population (blood donors), the difference was even more significant (P = 0.0004). When genotypes of all alcoholics (n = 123) were compared with genotypes of matched controls, the odds ratio (OR) for alcoholism for those subjects having the LL genotype vs those with HH genotype was 2.51, 95% CI 1.22-5.19, P = 0.006. Also, L allele frequency was significantly higher among alcoholics when compared with controls (P = 0.009). The estimate for population etiological (attributable) fraction for the LL genotype in alcoholism was 13.3% (95% CI 2.3-25.7%). The results indicate that the COMT polymorphism contributes significantly to the development of late-onset alcoholism." [Abstract]

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Recent Bipolar Disorder & Substance Abuse Research
1) Quello SB, Brady KT, Sonne SC
Mood disorders and substance use disorder: a complex comorbidity.
Sci Pract Perspect. 2005 Dec;3(1):13-21.
Mood disorders, including depression and bipolar disorders, are the most common psychiatric comorbidities among patients with substance use disorders. Treating patients' co-occurring mood disorders may reduce their substance craving and taking and enhance their overall outcomes. A methodical, staged screening and assessment can ease the diagnostic challenge of distinguishing symptoms of affective disorders from manifestations of substance intoxication and withdrawal. Treatment should maximize the use of psychotherapeutic interventions and give first consideration to medications proven effective in the context of co-occurring substance abuse. Expanded communication and collaboration between substance abuse and mental health providers is crucial to improving outcomes for patients with these complex, difficult co-occurring disorders. [PDF] [Free Full Text] [PubMed Citation] [Order full text from Infotrieve]

2) Gaudiano BA, Uebelacker LA, Miller IW
Impact of remitted substance use disorders on the future course of bipolar I disorder: Findings from a clinical trial.
Psychiatry Res. 2008 Jul 15;160(1):63-71.
Given the high lifetime prevalence rates of bipolar disorder and comorbid substance use disorders (SUDs), the aim of the study was to examine the effect of a remitted SUD on the future course of bipolar I disorder in patients taking part in a clinical trial. Patients with bipolar I disorder were enrolled in a larger study examining the effects of pharmacotherapy plus family interventions. These patients were recruited during an acute mood episode and their mood symptoms and substance abuse were assessed longitudinally for up to 28 months. Patients with a remitted SUD showed a poorer acute treatment response, a longer time to remission of their acute mood episode, and a greater percentage of time with subthreshold but clinically significant depression and manic symptoms over follow-up compared to those without this comorbidity pattern. Subsequent substance abuse during follow-up could not fully account for the poorer course of illness. As remitted SUDs appear to negatively predict treatment outcome, current findings have implications for both clinical trials of bipolar patients as well as clinical practice. [PubMed Citation] [Order full text from Infotrieve]

3) Talamo A, Baldessarini RJ, Centorrino F
Comparison of mania patients suitable for treatment trials versus clinical treatment.
Hum Psychopharmacol. 2008 May 19;
It remains uncertain whether bipolar disorder (BPD) patients in randomized-controlled trials (RCTs) are sufficiently representative of clinically encountered patients as to guide clinical-therapeutic practice. We complied inclusion/exclusion criteria by frequency from reports of 21 RCTs for mania, and applied them in a pilot study of patients hospitalized for DSM-IV BPD manic/mixed states to compare characteristics and clinical responses of patients who did versus did not meet exclusion criteria. From 27 initially identified inclusion/exclusion criteria ranked by citation frequency, we derived six inclusion, and 10 non-redundant-exclusion factors. Of 67 consecutive patients meeting inclusion criteria, 15 (22.4%) potential "research subjects" met all 10 exclusion criteria. The remaining 52 "clinical patients" differed markedly on exclusion criteria, including more psychiatric co-morbidity, substance abuse, involuntary hospitalization, and suicide attempts or violence, but were otherwise similar. In both groups responses to clinically determined inpatient treatments were similar, including improvement in mania ratings. Based on applying reported inclusion/exclusion criteria for RCTs to a pilot sample of hospitalized-manic patients, those likely to be included in modern RCTs were similar to patients who would be excluded, most notably in short-term antimanic-treatment responses. The findings encourage further comparisons of subjects included/excluded from RCTs to test potential clinical generalizability of research findings. The pilot study is limited in numbers and exposure times with which to test for the minor differences between "research subjects" and "clinical patients." Copyright (c) 2008 John Wiley & Sons, Ltd. [PubMed Citation] [Order full text from Infotrieve]

4) Melhem NM, Walker M, Moritz G, Brent DA
Antecedents and sequelae of sudden parental death in offspring and surviving caregivers.
Arch Pediatr Adolesc Med. 2008 May;162(5):403-10.
OBJECTIVES: To examine the psychiatric antecedents that put parents at risk for early death, and the psychological sequelae of bereavement in offspring and caregivers. DESIGN: A population-based study. SETTING: Bereaved families were recruited through the coroner's records and by advertisement. Control families were recruited by random-digit dialing and advertisement. PARTICIPANTS: Families with biological offspring from 7 to 25 years of age in which 1 parent died of suicide, accident, or sudden natural death were included (n = 140). Controls (n = 99) had 2 living parents and their biological offspring and had no death of a first-degree relative within the past 2 years. MAIN OUTCOME MEASURES: Lifetime psychiatric history for deceased parents (probands) and new-onset psychiatric disorders, self-reported symptoms, and functional status in offspring and surviving caregivers. RESULTS: Bipolar disorder, substance abuse, and personality disorders are more common in probands who died of suicide or accident than in control parents. Bereaved offspring and their caregivers were at increased risk for depression and posttraumatic stress disorder. Bereaved offspring had a 3-fold (95% confidence interval, 1.3-7.0) increased risk of depression, even after controlling for antecedent and concomitant risk factors. Offspring bereaved by suicide showed similar outcomes compared with those bereaved by other types of death. CONCLUSIONS: Bereavement conveys an increased risk of depression and posttraumatic stress disorder above and beyond other vulnerability factors. Better integration of medical and psychiatric care may prevent premature parental death, but once it occurs, physicians should be alert to the increased risk for depression and posttraumatic stress disorder in bereaved offspring and their caregivers. [Free Full Text] [PubMed Citation] [Order full text from Infotrieve]

5) Shi J, Badner JA, Hattori E, Potash JB, Willour VL, McMahon FJ, Gershon ES, Liu C
Neurotransmission and bipolar disorder: A systematic family-based association study.
Am J Med Genet B Neuropsychiatr Genet. 2008 Apr 28;
Neurotransmission pathways/systems have been proposed to be involved in the pathophysiology and treatment of bipolar disorder for over 40 years. In order to test the hypothesis that common variants of genes in one or more of five neurotransmission systems confer risk for bipolar disorder, we analyzed 1,005 tag single nucleotide polymorphisms in 90 genes from dopaminergic, serotonergic, noradrenergic, GABAergic, and glutamatergic neurotransmitter systems in 101 trios and 203 quads from Caucasian bipolar families. Our sample has 80% power to detect ORs >/= 1.82 and >/=1.57 for minor allele frequencies of 0.1 and 0.5, respectively. Nominally significant allelic and haplotypic associations were found for genes from each neurotransmission system, with several reaching gene-wide significance (allelic: GRIA1, GRIN2D, and QDPR; haplotypic: GRIN2C, QDPR, and SLC6A3). However, none of these associations survived correction for multiple testing in an individual system, or in all systems considered together. Significant single nucleotide polymorphism associations were not found with sub-phenotypes (alcoholism, psychosis, substance abuse, and suicide attempts) or significant gene-gene interactions. These results suggest that, within the detectable odds ratios of this study, common variants of the selected genes in the five neurotransmission systems do not play major roles in influencing the risk for bipolar disorder or comorbid sub-phenotypes. (c) 2008 Wiley-Liss, Inc. [PubMed Citation] [Order full text from Infotrieve]

6) Antshel KM, Khan FM
Is there an increased familial prevalence of psychopathology in children with nonverbal learning disorders?
J Learn Disabil. 2008 May-Jun;41(3):208-17.
The cognitive and behavioral symptoms of nonverbal learning disabilities (NLD) have been described by previous investigators. Nevertheless, we know far less about the potential genetic contributions that may predispose a child to have NLD. An endophenotype model was investigated in 5 samples of children ages 9 to 15 years: NLD (n = 32); reading disorders (RD; n = 59); participants with a psychiatric diagnosis but without a learning disability (n = 55); typically developing controls (n = 31); and children with velocardiofacial syndrome (VCFS), a chromosomal deletion syndrome that has been proposed as being an exemplar of NLD (VCFS + NLD; n = 20). Based on a family genetic interview, the authors' data suggest that children with NLD, RD, or a psychiatric diagnosis have a higher prevalence rate of attention-deficit/hyperactivity disorder (ADHD) and substance abuse/dependence. Psychiatric controls and children with NLD--but not children with RD-- showed higher prevalence rates of familial bipolar disorder. [PubMed Citation] [Order full text from Infotrieve]

7) van Rossum I, Haro JM, Tenback D, Boomsma M, Goetz I, Vieta E, van Os J
Stability and treatment outcome of distinct classes of mania.
Eur Psychiatry. 2008 Apr 21;
BACKGROUND: Psychopathological heterogeneity in manic syndromes may in part reflect underlying latent classes with characteristic outcome patterns. Differential treatment course and outcome after 12 weeks of treatment were examined for three distinct classes of patients with acute mania in bipolar disorder. SUBJECTS AND METHODS: Three thousand four hundred and twenty-five patients with acute mania were divided into three distinct mania classes: 'Typical', 'Psychotic' and 'Dual' (i.e. comorbid substance use) mania. Persistence of class differences and social outcomes were examined, using multilevel regression analyses and odds ratios. RESULTS: The three classes showed substantial stability post-baseline in the pattern of associations with class-characteristic variables. Psychotic and Dual mania predicted poorer outcome in terms of psychosis comorbidity and overall bipolar and mania severity, while Dual mania additionally predicted poorer outcome of alcohol and substance abuse. Worse social outcomes were observed for both Dual and Psychotic mania. CONCLUSION: The identified distinct classes are stable and associated with differential treatment outcome. Overall, Dual and Psychotic mania show less favourable outcomes compared to Typical mania. These findings additionally give rise to concern on the generalisability of randomized clinical trials RCTs. [PubMed Citation] [Order full text from Infotrieve]

8) Muroff J, Edelsohn GA, Joe S, Ford BC
The role of race in diagnostic and disposition decision making in a pediatric psychiatric emergency service.
Gen Hosp Psychiatry. 2008 May-Jun;30(3):269-76.
OBJECTIVE: We investigated the influence of race/ethnicity in diagnostic and disposition decision-making for children and adolescents presenting to an urban psychiatric emergency service (PES). METHOD: Medical records were reviewed for 2991 child and adolescent African-American, Hispanic/Latino and white patients, treated in an urban PES between October 2001 and September 2002. A series of bivariate and binomial logistic regression analyses were used to delineate the role of race in the patterns and correlates of psychiatric diagnostic and treatment disposition decisions. RESULTS: Binomial logistic regression analyses reveal that African-American (OR=2.28, P<.001) and Hispanic/Latino (OR=2.35, P<.05) patients are more likely to receive psychotic disorders and behavioral disorders diagnoses (African American: OR=1.66, P<.001; Hispanic/Latino: OR=1.36, P<.05) than white children/adolescents presenting to PES. African-American youth compared to white youth are also less likely to receive depressive disorder (OR=0.78, P<.05), bipolar disorder (OR=.44, P<.001) and alcohol/substance abuse disorder (OR=.18, P<.01) diagnoses. African-American pediatric PES patients are also more likely to be hospitalized (OR=1.50, P<.05), controlling for other sociodemographic and clinical factors (e.g., Global Assessment of Functioning). CONCLUSIONS: The results highlight that nonclinical factors such as race/ethnicity are associated with clinical diagnostic decisions as early as childhood suggesting the pervasiveness of such disparities. [PubMed Citation] [Order full text from Infotrieve]

9) Saatcioglu O, Tomruk NB
Practice of electroconvulsive therapy at the research and training hospital in Turkey.
Soc Psychiatry Psychiatr Epidemiol. 2008 Apr 21;
OBJECTIVE: We sought to obtain an overview of electroconvulsive therapy (ECT) practice in Bakirkoy Research and Training Hospital for Psychiatric and Neurological Diseases, which is the biggest hospital for psychiatry in Turkey. METHOD: From 1st January 2006 to 30th June 2007, a form enquiring about evaluation of ECT was filled retrospectively. RESULTS: The total number of patients, admitted for psychiatry during the survey period was 265,283. A total of 1,531 patients (12.4% among inpatients and 0.58% in all psychiatric admissions) received 13,618 sessions (including multiple hospitalizations) of ECT from 12,341 psychiatric inpatients during the survey period. Ninety-eight patients had multiple hospitalizations. The male-to-female ratio was 1.26-1. Patients with bipolar affective disorder, current episode manic with or without psychotic symptoms received ECT most frequently (30.3%), followed by patients with schizophrenia (29.5%), severe depressive episode with or without psychotic symptoms (include bipolar affective disorder current episode severe depression) (15.2%), other non-organic psychotic disorders (14.4%), schizoaffective disorders (6.3%), mental and behavioral disorders due to psychoactive substance abuse with psychotic disorders (3.5%) and catatonic schizophrenia (0.7%). Patients who received ECT were in age group of 25-44 years (64.7%), followed by 45-64 years (17.7%), 18-24 years (15.4%), 65 years and older (1.4%), and younger than 18 years (0.8%). All patients received modified ECT. There were no ECT-related deaths during the survey. CONCLUSION: The rate of ECT among all psychiatric inpatients during the survey period was 12.4%. The majority of patients who received ECT were diagnosed with bipolar affective disorder-current episode manic and schizophrenia. ECT training programs for psychiatry residents and specialists should be planned, and conducted systematically. [PubMed Citation] [Order full text from Infotrieve]

10) Martinotti G, Andreoli S, Di Nicola M, Di Giannantonio M, Sarchiapone M, Janiri L
Quetiapine decreases alcohol consumption, craving, and psychiatric symptoms in dually diagnosed alcoholics.
Hum Psychopharmacol. 2008 Jul;23(5):417-24.
AIMS: Patients with dual diagnosis are often excluded from clinical trials although more than half of all individuals with Bipolar Disorder have a substance abuse problem at some point in their lifetime, representing a high-risk clinical population. The purpose of this study was to investigate the safety and efficacy of quetiapine in the treatment of alcohol dependence comorbid with disorders characterized by high levels of mood and behavioral instability. METHODS: Twenty-eight subjects, after a detoxification period, were orally treated with flexible doses of quetiapine for 16 weeks. At each assessment patients were evaluated through the Obsessive Compulsive Drinking Scale (OCDS), the Visual Analogue Scale (VAS) for craving, the Clinical Institute Withdrawal Assessment for Alcohol (CIWA-Ar), the Brief Psychiatric Rating Scale (BPRS), the Hamilton Depression Rating Scale (HDRS), the Young Mania Rating Scale (YMRS), and the Clinical Global Impression (CGI) scale. RESULTS: Forty-three percent of patients remained totally alcohol free, 32% patients relapsed, with an average of 15.4 drinking days in the period of the study (112 days) and 25% dropped-out. Significant reductions from baseline to exit were observed in the OCDS, VAS, BPRS, HDRS, and number of drinking days per week. Changes in alcohol craving correlated with psychiatric symptoms as to BPRS and HDRS, with the highest level of correlation evidenced for the HDRS items of insomnia. DISCUSSION: In this open-label study, quetiapine decreased alcohol consumption, craving for alcohol, and psychiatric symptoms intensity, maintaining a good level of tolerance. A strength of this study is that the use of quetiapine was not adjunctive with other pharmacological and non-pharmacological treatment. Double-blind placebo-controlled studies are required with a larger study population to confirm these data. In the meantime, for a select group of psychiatric patients, quetiapine may offer some advantages in preventing relapse. [PubMed Citation] [Order full text from Infotrieve]

11) Rank MG, Chaffin I, Figley CR, Lawrence T
The treatment of posttraumatic stress disorder in an extended care psychiatric rehabilitation program.
Work. 2008;30(2):113-21.
This research study intended to determine which patient diagnostic group benefited most from an extended care psychiatric rehabilitation program (Program). Archival data were used to assess the completion rates among those subjected to one or more of the Program's treatment modalities. A correlational design was used to determine whether demographic or diagnostic variables were related to program completion. The results indicate that patients with a diagnosis of posttraumatic stress disorder or bipolar disorder are the most likely diagnostic groups to benefit from participation in an extended care psychiatric rehabilitation program. Those patients with a diagnosis of schizophrenia or substance abuse may not be appropriate for this type of treatment program, and in this study, were the least likely to benefit. [PubMed Citation] [Order full text from Infotrieve]

12) Gamma A, Angst J, Ajdacic-Gross V, R�ssler W
Are hypomanics the happier normals?
J Affect Disord. 2008 Apr 9;
BACKGROUND: Not much is known about hypomanic states in subjects free of major and minor depressive mood disorders. Our aim was to identify and characterise a group of such "pure" hypomanics in relation to a normal control group. METHODS: Data were obtained from the Swiss Zurich study, a stratified epidemiological sample of young adults from the general population, followed from age 20 to 40. "Pure" hypomania was defined as a period of increased activity and decreased need for sleep with consequences (e.g. legal trouble or reactions by others). Minor and major mood disorders were excluded. RESULTS: Twenty-three subjects were identified as pure hypomanics. They overlapped minimally with and were clearly different from subjects with DSM-IV defined hypomanic episodes, most of whom had a bipolar disorder. Pure hypomanics were characterised by physical and social overactivity, elevated and irritable mood, as well as increases in extraversion, sexual interest, and risk-taking behaviors. They had higher monthly incomes and were more often married than controls. Subjective distress due to hypomanic symptoms was virtually absent. Quality of life and treatment rates for mood and anxiety were not different from controls, although sleep disturbances, substance abuse and binge eating were more frequent. LIMITATIONS: The subsample identified was small. Due to the focus of the study on pathology, some positive aspects of hypomania may have been missed. CONCLUSIONS: The existence of a group of pure hypomanics presenting a mixed picture of clinically relevant and irrelevant characteristics supports the concept of a continuum from normal to pathological mood states. [PubMed Citation] [Order full text from Infotrieve]

13) Gaudiano BA, Weinstock LM, Miller IW
Improving treatment adherence in bipolar disorder: a review of current psychosocial treatment efficacy and recommendations for future treatment development.
Behav Modif. 2008 May;32(3):267-301.
Treatment adherence is a frequent problem in bipolar disorder, with research showing that more than 60% of bipolar patients are at least partially nonadherent to medications. Treatment nonadherence is consistently predictive of a number of negative outcomes in bipolar samples, and the discontinuation of mood stabilizers places these patients at high risk for relapse. Several types of adjunctive treatment (family, psychoeducational, cognitive-behavioral) have been investigated for improving symptoms and functioning in bipolar patients with some success. To date, less attention has been paid to developing treatments specifically to promote treatment adherence to and engagement with pharmacological as well as behavioral treatments in patients with bipolar disorder. First, we review the effects of adjunctive interventions specifically on treatment adherence outcomes in 14 published clinical trials. Based on this empirical knowledge base, we present a preliminary description of the treatment strategies that appear most promising for improving adherence. The article also provides research recommendations for developing more effective interventions for the purpose of improving bipolar treatment adherence. Finally, special treatment considerations, including the potential impact of comorbid substance abuse and bipolar depression, are discussed. [PubMed Citation] [Order full text from Infotrieve]

14) Madeira C, Freitas ME, Vargas-Lopes C, Wolosker H, Panizzutti R
Increased brain D-amino acid oxidase (DAAO) activity in schizophrenia.
Schizophr Res. 2008 Apr;101(1-3):76-83.
D-serine has been shown to be a major endogenous coagonist of the N-methyl D-aspartate (NMDA) type of glutamate receptors. Accumulating evidence suggests that NMDA receptor hypofunction contributes to the symptomatic features of schizophrenia. d-serine degradation can be mediated by the enzyme d-amino acid oxidase (DAAO). An involvement of d-serine in the etiology of schizophrenia is suggested by the association of the disease with single nucleotide polymorphisms in the DAAO and its regulator (G72). The present study aims to further elucidate whether the DAAO activity is altered in schizophrenia. Specific DAAO activity was measured in postmortem cortex samples of bipolar disorder, major depression and schizophrenia patients, and normal controls (n=15 per group). The mean DAAO activity was two-fold higher in the schizophrenia patients group compared with the control group. There was no correlation between DAAO activity and age, age of onset, duration of disease, pH of the tissue and tissue storage time and no effect of gender, cause of death and history of alcohol and substance abuse. The group of neuroleptics users (including bipolar disorder patients) showed significantly higher D-amino acid oxidase activity. However, there was no correlation between the cumulative life-time antipsychotic usage and D-amino acid oxidase levels. In mice, either chronic exposure to antipsychotics or acute administration of the NMDA receptor blocker MK-801, did not change d-amino acid oxidase activity. These findings provide indications that D-serine availability in the nervous system may be altered in schizophrenia because of increased D-amino acid degradation by DAAO. [PubMed Citation] [Order full text from Infotrieve]

15) Buckley PF
Update on the treatment and management of schizophrenia and bipolar disorder.
CNS Spectr. 2008 Feb;13(2 Suppl 1):1-10; quiz 11-2.
Schizophrenia and bipolar disorder are two debilitating mental health disorders, both of which manifest early in adulthood and are associated with severe impairment as well as increased suicide risk. In addition, factors affecting disease severity, such as substance abuse, are often prevalent in these patient populations. In the United States, the prevalence of bipolar disorder is believed to be approximately 3.5%, while the rate for schizophrenia is approximately 1%. Although each disorder presents with its own symptom profile, the approaches to treatment are similar and include early diagnosis and use of psychosocial therapy. Research initiatives, such as genetic studies, are used in both disorders as well. For schizophrenia, treatment typically includes the combination of an antipsychotic and psychosocial intervention. For bipolar disorder, clinicians commonly prescribe mood-stabilizing drugs (eg, lithium, valproic acid) as first-line treatment. Many of the second-generation antipsychotics have been approved by the US Food and Drug Administration for bipolar disorder treatment in the manic phase. Patients who are affected by either disorder also face the challenges of treatment nonadherence, which can be affected by substance abuse and can hinder symptom remission as well as spur unnecessary medication switches due to nonresponse. Family members play a key role in the treatment of either disorder. This expert review supplement focuses on treatment options and research strategies being utilized for the management and advanced understanding of schizophrenia and bipolar disorder. Research examining the pharmacology of commonly used medications for the treatment of both disorders is also presented. [PubMed Citation] [Order full text from Infotrieve]

16) Hanley MJ, Kenna GA
Quetiapine: treatment for substance abuse and drug of abuse.
Am J Health Syst Pharm. 2008 Apr 1;65(7):611-8.
PURPOSE: The use of quetiapine as a drug to treat various substance use disorders as well as a drug of abuse is examined. SUMMARY: Quetiapine's effectiveness in treating schizophrenia and bipolar disorder is well-known; however, growing evidence has indicated that it may be useful in the treatment of various substance use disorders. Small-scale studies have been conducted to investigate the potential benefit of quetiapine in patients dependent on alcohol, cocaine, and amphetamines. The results of these two studies provide some evidence that quetiapine may benefit patients diagnosed with a mental illness who are also dependent on cocaine, amphetamines, or both, though more rigorous studies are needed. An unforeseen use of antipsychotics, specifically quetiapine, as drugs of abuse has emerged. Since antipsychotics are not classified as controlled substances, the majority of clinicians may not consider the diversion of antipsychotics for recreational purposes, but evidence of this is increasing, particularly in incarcerated individuals. Intravenous quetiapine abuse was first reported in the literature in 2005. Although most cases of quetiapine abuse have been reported in the correctional setting, inappropriate quetiapine use within the community has been documented. Thus far, all of the documented cases have involved patients with a prior history of substance abuse. Clinicians must be cognizant of the potential for quetiapine as a treatment for substance use disorders and as a drug of abuse. CONCLUSION: Quetiapine is a promising treatment for substance use disorders alone or combined with other psychiatric diagnoses, such as bipolar disorder and schizophrenia. Quetiapine abuse has also been documented, particularly in the correctional setting. [PubMed Citation] [Order full text from Infotrieve]

17) L�pez J, Baca E, Botillo C, Quintero J, Navarro R, Negueruela M, P�rez M, Basurte I, Fern�ndez A, Jim�nez M, Gonz�lez J
Diagnostic errors and temporal stability in bipolar disorder.
Actas Esp Psiquiatr. 2008 Mar 17;
The diagnosis of bipolar disorder is frequently modified during the course of the illness. Diagnostic changes and associated errors are described for 1,153 patients diagnosed as bipolar disorder, aged over 18 years and with at least ten follow-up visits. Data was extracted from a clinical registry of out-patient care specialized in Psychiatry and psychiatric hospitalizations of 25,152 patients representative of an urban area of 240,000 inhabitants. Limit for diagnostic stability was established as the maintenance of the bipolar disorder diagnosis in at least 75% of the visits. A total of 158 (46.1%) out of 342 patients diagnosed as having a bipolar disorders in the first visit kept this diagnostic constant in subsequent evaluations. Infradiagnostic initial error was committed with 108 stable patients who were not diagnosed in the first visit. 184 patients diagnosed in the first visit with bipolar disorder had less than 75% concordant diagnosis along the follow-up and could be considered as initial overdiagnosis. Two hundred and nine out of the 443 patients who were diagnosed as bipolar disorder in their last visit did not keep stability criteria in their follow-up and could be considered therefore as final overdiagnosis. Thirty two stable patients not diagnosed in their last visit could be considered as infradiagnosis final error. Diagnosis from schizophrenia spectrum (F2) appears in one of every four psychiatric visits of the patients included in this study. Overlap was seen in three other categories: anxiety disorders (F4), personality disorders (F6) and substance abuse disorders. Conclusion. Initial course of bipolar disorder causes difficulties in the diagnosis. Key words: Bipolar disorder. Stability. Diagnosis. Course. Actas Esp Psiquiatr 2008;36(0):00-00. [PubMed Citation] [Order full text from Infotrieve]

18) Stasiewicz PR, Vincent PC, Bradizza CM, Connors GJ, Maisto SA, Mercer ND
Factors affecting agreement between severely mentally ill alcohol abusers' and collaterals' reports of alcohol and other substance abuse.
Psychol Addict Behav. 2008 Mar;22(1):78-87.
This study examined subject-collateral reports of alcohol use among a sample of 167 dually diagnosed individuals seeking outpatient treatment at a community mental health clinic. All subjects met Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) criteria for a schizophrenia-spectrum or bipolar disorder and for alcohol abuse or dependence. Subjects were recruited within 2 weeks of treatment entry and completed measures of cognitive functioning, alcohol dependence severity, psychiatric symptoms, and quantity and frequency of substance use over the previous 60 days using the Timeline Follow-Back interview (L. C. Sobell & M. B. Sobell, 1996). They also provided a urine sample, which was screened for recent drug use. Collateral interviews were conducted by phone and included an assessment of the subject's alcohol and drug use over the same 60-day period. Collaterals also reported their confidence in the accuracy of their reports. Overall, the results indicated generally poor subject-collateral agreement. However, subject-collateral agreement appeared better for those individuals (n = 97) with negative urine drug screens. The most consistent predictor of subject-collateral discrepancy scores was subjects' recent drug use. Recommendations for enhancing the validity of self-reports of substance use in a severely mentally ill population are discussed. [PubMed Citation] [Order full text from Infotrieve]

19) Berk M, Ng F, Wang WV, Tohen M, Lubman DI, Vieta E, Dodd S
Going up in smoke: Tobacco smoking is associated with worse treatment outcomes in mania.
J Affect Disord. 2008 Feb 14;
BACKGROUND: This study aimed to compare the treatment responses between smokers and non-smokers in bipolar mania clinical trials. METHODS: Post-hoc analysis was conducted on data collected from three double-blind, randomised controlled trials in bipolar mania that had similar inclusion criteria. Patients were randomised to olanzapine (N=70) or placebo (N=69) for 3 weeks in Trial 1, olanzapine (N=234) or haloperidol (N=216) for 12 weeks in Trial 2, and olanzapine (N=125) or divalproex (N=126) for 47 weeks in Trial 3. This study analysed the Young Mania Rating Scale (YMRS) total scores and Clinical Global Impressions scale for bipolar disorder (CGI-BP) mania severity scores between smokers and non-smokers for each trial and for the pooled data from all three trials, using a mixed-effects model repeated measures approach. RESULTS: For the pooled data, non-smokers showed superior treatment outcomes on both the YMRS (P=0.002) and CGI-BP (P<0.001), as well as longer time to discontinuation for any cause utilising Kaplan-Meier survival curves. For the individual trials, non-smokers showed greater improvement than smokers on both CGI-BP and YMRS in both treatment arms of Trial 2 (CGI-BP: haloperidol P=0.011, olanzapine P=0.042; YMRS: haloperidol P=0.010, olanzapine P=0.019), and in the olanzapine arm of Trial 3 (CGI-BP: P=0.002; YMRS: P=0.006). No significant difference in outcomes was found between smokers and non-smokers in Trial 1. LIMITATIONS: Post-hoc design, categorical definition of smoking status, unavailable antipsychotic drug levels, confounding effects of trial medications and substance abuse. CONCLUSIONS: Smoking appears to be associated with worse treatment outcomes in mania. [PubMed Citation] [Order full text from Infotrieve]

20) Garno JL, Gunawardane N, Goldberg JF
Predictors of trait aggression in bipolar disorder.
Bipolar Disord. 2008 Mar;10(2):285-92.
OBJECTIVES: Although aggressive behavior has been associated with bipolar disorder (BD), it has also been linked with developmental factors and disorders frequently found to be comorbid with BD, making it unclear whether or not it represents an underlying biological disturbance intrinsic to bipolar illness. We therefore sought to identify predictors of trait aggression in a sample of adults with BD. METHODS: Subjects were 100 bipolar I (n = 73) or II (n = 27) patients consecutively evaluated in the Bipolar Disorders Research Program of the New York Presbyterian Hospital-Payne Whitney Clinic. Diagnoses were established using the Structured Clinical Interview for the DSM-IV (SCID-I) and Cluster B sections of the SCID-II. Mood severity was rated by the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS). Histories of childhood maltreatment were assessed via the Childhood Trauma Questionnaire (CTQ), while trait aggression was measured by the Brown-Goodwin Aggression Scale (BGA). RESULTS: In univariate analyses, significant relationships were observed between total BGA scores and CTQ total (r = 0.326, p = 0.001), childhood emotional abuse (r = 0.417, p < 0.001), childhood physical abuse (r = 0.231, p = 0.024), childhood emotional neglect (r = 0.293, p = 0.004), post-traumatic stress disorder (t = -2.843, p = 0.005), substance abuse/dependence (t = -2.914, p = 0.004), antisocial personality disorder (t = -2.722, p = 0.008) and borderline personality disorder (t = -5.680, p < 0.001) as well as current HDRS (r = 0.397, p < 0.001) and YMRS scores (r = 0.371, p < 0.001). Stepwise multiple regression revealed that trait aggression was significantly associated with: (i) diagnoses of comorbid borderline personality disorder (p < 0.001); (ii) depressive symptoms (p = 0.001); and (iii) manic symptoms (p < 0.001). CONCLUSIONS: Comorbid borderline personality disorder and current manic and depressive symptoms each significantly predicted trait aggression in BD, while controlling for confounding factors. The findings have implications for nosologic distinctions between bipolar and borderline personality disorders, and the developmental pathogenesis of comorbid personality disorders as predisposing to aggression in patients with BD. [PubMed Citation] [Order full text from Infotrieve]