A Review of the Literature of Mirtazapine in Co-Occurring Depression and an Alcohol Use Disorder.

BACKGROUND: Prior medication studies involving individuals with major depression in combination with an alcohol use disorder (MDD/AUD) have mainly focused on SSRI and tricyclic antidepressants, with generally ineffective results. Consequently, effective treatments for that common comorbid condition remain elusive. Mirtazapine is an antidepressant medicine with a unique pharmacological profile, whose effectiveness for treating non-comorbid depression reportedly may exceed that of SSRIs. OBJECTIVE/METHODS: We now review the published literature regarding the tolerability and efficacy of mirtazapine for the treatment of the depression and the pathological alcohol ingestion of individuals with co-occurring MDD/AUD, including a review of four of our own small studies and two studies conducted outside the United States. RESULTS/CONCLUSIONS: The findings of these studies suggest that mirtazapine is well tolerated among persons with comorbid MDD/AUD. Results also provide some evidence of efficacy for mirtazapine for decreasing the level of depression of persons with co-occurring MDD/AUD, and suggest that decreases in depression may occur relatively quickly after starting treatment, but provide no evidence of effectiveness for decreasing the level of alcohol ingestion. Large-scale double-blind, placebo-controlled studies are warranted to further clarify the tolerability and efficacy of mirtazapine among individuals with MDD/AUD.

Predictive validity of the physical disorders axis of the DSM multiaxial diagnostic system.

This paper reports on the predictive validity of the physical disorders axis (axis III) of the DSM multiaxial diagnostic system at 3-year follow-up. A total of 515 general psychiatric patients were assessed with a semistructured procedure that covers all DSM-III diagnoses and axes, and were subsequently followed up for 3 years. Outcome was assessed with several measures of adaptive functioning. Baseline axis III was analyzed according to a) presence of any physical disorder, b) the number of these, c) presence of major chronic physical disorders (MCPD), and d) the number of these. Prediction of impairment in functioning (Strauss-Carpenter Scale), derived from baseline axis III, ranged from a correlation coefficient of .18 when expressed as the presence of any physical disorder to .35 when represented by the number of MCPD. Furthermore, within patients with specific psychiatric disorders, it was found that number of MCPD reached a predictive validity of .55 for patients with dysthymic disorders, .44 for those with anxiety disorders, and .41 for those with major depression. Comparative multiple regression analyses, controlling for demographic and clinical variables, showed that the number of MCPD at baseline was the most important predictor of functioning outcome among patients with dysthymic disorders and major depression. The number of MCPD experienced by general psychiatric patients seems to be an important predictor of future functioning, particularly for patients with certain psychiatric disorders. This points out the importance of considering the relationship between psychiatric and MCPD when conducting systematic clinical assessments towards the prediction of course and outcome.

Concordance between verbal report and urine screen of recent marijuana use in adolescents.

This study compared the concordance of self-report for recent marijuana use with results obtained from urine drug screen. The sample consisted of adolescent sons of fathers with DSM-III-R lifetime substance use disorder (SUD) [high average risk (HAR); N= 75] and sons of fathers with no Axis 1 psychiatric or SUD [low average risk (LAR); N= 125]. To avoid recall bias, and to ensure that the timeframe for accurate detection was restricted to promote accuracy, urine drug screen results were compared to self-reported marijuana use during the prior 48 h using an interview format. The HAR group of adolescents reported a higher rate of recent cannabis use and also had a higher rate of cannabis detection as measured in urine. The two groups did not differ with respect to either over or under-reporting marijuana use. Overall, of 19 participants who obtained positive urine cannabis results, six (31.5%) verbally denied that they used marijuana within the previous 2 days. Among the 181 participants who obtained a negative urine drug screen, 20 subjects (11.5%) inaccurately asserted that they had used marijuana within the prior 2 days. In total, 13% of the participants (26/200) inaccurately reported recent cannabis use. These results underscore the need for caution in interpreting the results of self-report methods documenting the prevalence of drug use among youth.

Characterizing female bipolar alcoholic patients presenting for initial evaluation.

This study examined gender differences of age and race-matched group of bipolar disorder (BPO) patients with comorbid alcohol dependence (AD; n = 65; males = 35, females = 30) to a group of BPO patients without comorbid AD (n = 61; males = 22, females = 39). The two groups were also similar on marital status and frequency of BPO subtypes. The results revealed that female bipolar alcoholic patients were more likely to report depressive symptoms as compared to either male bipolar alcoholics or both male and female non-alcoholic bipolar patients. When compared to male bipolar alcoholics, they had higher frequency of depressed mood, slow motor behavior, low self-esteem, decreased libido, decreased appetite, and higher general anxiety symptoms. On the other hand, female bipolar alcoholics differed from female non-alcoholic bipolar patients on reports of mood lability, depressed mood, low self-esteem, suicidal indicators, decreased libido, and general anxiety symptoms. These results raise the question of whether alcohol increases the frequency of depressive symptoms among female bipolar patients.

Correlates of mental health service utilization and unmet need among a sample of male adolescents.

The authors sought to identify the correlates of mental health services utilization and unmet need for these services among a sample of adolescent males. We hypothesized that our findings would replicate and extend those of the recent Methods for the Epidemiology of Child and Adolescent Mental Disorders (MECA) study, which found that parental factors play a major role in their children's unmet mental health care needs. Our study involved an evaluation of mental health service utilization and unmet need during the prior 2 years, as reported by the subjects at a follow-up assessment at age 16. Four factors were found to predict increased mental health services utilization, including attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) among the adolescent males, the father's alcohol use disorder, and the mother's amphetamine use disorder. One factor was found to predict decreased utilization, the father's cannabis use disorder. Four factors significantly predicted unmet treatment need, including conduct disorder, the mother's amphetamine use disorder, a higher number of siblings, and a parental history of having had a childhood anxiety disorder. The results of this study suggest that parental psychopathology, parental substance abuse, the presence of conduct disorder, and an increased number of siblings act as barriers to adequate mental health treatment among adolescents. These findings confirm the crucial role that parental factors play in the treatment utilization and the unmet treatment need of their children, and also suggest that an increased number of siblings can also be associated with unmet treatment need.

Impact of parental substance use disorder and child neglect severity on substance use involvement in male offspring.

Two child self-report scales were developed to measure parental neglect (emotional distance and parental involvement) in a sample of 344 boys between 10 and 12 years of age. Psychometric analyses of the parental emotional distance and involvement scales demonstrated their unidimensionality; construct, concurrent, and predictive validity; and reliability. Cross-sectional analyses indicated that neglect was more severe among boys who had a parent with a DSM-III-R lifetime substance use disorder (SUD) compared to youth whose parents had no Axis I psychiatric disorder. In addition, children reported more severe neglect by the mother than the father. Longitudinal analyses of a subsample (n = 99) revealed that child neglect at ages 10-12 predicted significant variance on a composite measure of substance use involvement and severity of substance use as well as increased the risk for SUD at age 19.

DSM-IV learning disorders in 10- to 12-year-old boys with and without a parental history of substance use disorders.

This research examined whether learning disorders (LDs) among 10- to 12-year-old boys are related to a parental history of alcohol and other substance use disorders (SUDs). Subjects were boys with (SA+; n = 179) and without (SA-; n = 203) a parental history of SUDs. LD diagnoses were made according to DSM-IV criteria using several standardized intelligence tests, and mother and teacher reports of academic and cognitive difficulties. The results indicated a higher rate of DSM-IV LDs in SA+ compared to SA- boys. This association remained significant after accounting for the effects of socioeconomic status and ethnicity. SA+ boys with a lower socioeconomic status had particularly high rates of LDs (15.3%). The results suggest that LDs are associated with a parental history of SUDs. SA+ children with lower SES may be at particularly high risk for cognitive and academic difficulties.

Family and peer correlates of behavioral self-regulation in boys at risk for substance abuse.

Behavioral self-regulation (BSR), defined herein as the degree to which one can control one's own activity and reactivity to environmental stimuli, has been posited to be salient to the onset of adolescent substance abuse. The goal of this study was to clarify particular family and peer correlates of BSR in at-risk sons. Subjects were 10-through 12-year-old sons of substance-abusing fathers (high-average risk [HAR]; n = 176) and normal controls (low-average risk [LAR]; n = 199). A BSR latent trait was developed using multiple measures and multiple informants. Analyses included separate hierarchical linear regressions for HAR and LAR groups. In the hierarchical linear model for HAR sons, family dysfunction and deviant peer affiliation were significantly associated with BSR, whereas for LAR sons, only peer affiliation was significantly associated with BSR. The above family and peer correlates differed in proportions of variance explained for BSR in HAR and LAR sons. These findings extend previous studies by showing that, in a hierarchical linear model, BSR in HAR sons is associated with specific interpersonal, family, and peer factors. These findings suggest that empirical, theory-guided interventions to prevent worsening of BSR in HAR boys should address specific interpersonal, family, and peer factors.

Hormonal and behavioral homeostasis in boys at risk for substance abuse.

This study modeled the influences of cortisol reactivity, androgens, age-corrected pubertal status, parental personality, family and peer dysfunction on behavioral self-regulation (BSR), in boys at high (HAR) and low average risk (LAR) for substance abuse. Differences between risk groups in cortisol and androgen concentrations, and cortisol reactivity were also examined. Subjects were 10- through 12-year-old sons of substance abusing fathers (HAR; n = 150) and normal controls (LAR; n = 147). A multidimensional construct of BSR was developed which utilized multiple measures and multiple informants. Boys reported on family dysfunction and deviant behavior among their peers. Parents reported on their propensity to physically abuse their sons, and their own number of DSM-III-R Antisocial Personality Disorder symptoms. Endocrine measures included plasma testosterone, dihydrotestosterone, and salivary cortisol. HAR boys, compared to LAR boys, had lower mean concentrations for testosterone, dihydrotestosterone, salivary cortisol prior to evoked related potential testing, and lower cortisol reactivity. The number of maternal Antisocial Personality Disorder symptoms, parental potential for physical abuse, degree of family dysfunction, and peer delinquency were significantly associated with BSR. Parental aggression antisocial personality symptoms and parental physical abuse potential are likely to influence sons' behavioral dysregulation and homeostatic stress reactivity. These key components of liability are posited to increase the likelihood of developing suprathreshold Psychoactive Substance Use Disorder (PSUD).

Association between hyperactivity and executive cognitive functioning in childhood and substance use in early adolescence.

OBJECTIVE: To determine whether deficient executive cognitive functioning (ECF) in association with high behavioral activity level comprise components of the liability to substance abuse. METHOD: A high-risk (HR) group having fathers with a lifetime DSM-III-R diagnosis of a psychoactive substance use disorder was compared with a low-average-risk (LAR) group whose fathers had neither psychoactive substance use disorder nor another adult Axis I psychiatric disorder. ECF and behavioral activity were measured using neuropsychological tests, activity monitor, diagnostic interview, and informant ratings when the subjects were 10 to 12 years of age. Alcohol, tobacco, and cannabis use were measured at 2-year follow-up. RESULTS: At baseline, the HR group had a significantly higher behavioral activity level and exhibited poorer performance on ECF tests than the LAR group. By early adolescence, HR subjects had a higher lifetime rate of tobacco and cannabis use and earlier age at onset of cannabis use. ECF capacity, but not behavioral activity level, predicted tobacco and cannabis use, total number of drugs ever tried, and severity of drug involvement. ECF accounted for additional variance beyond the effects of conduct problems on these outcomes. CONCLUSION: Whereas behavioral activity and ECF capacity in late childhood distinguishes HR from LAR youth, childhood ECF capacity is the more salient predictor of drug use in early adolescence.

Child abuse potential in parents with histories of substance use disorder.

OBJECTIVE: To examine the relationship between parental history of substances use disorders (SUDs) and abuse potential. METHOD: Milner's (1986) Child Abuse Potential Inventory (CAPI) was administered to fathers and mothers (with and without histories of SUDs) of 10- to 12-year-old boys. RESULTS: Fathers and mothers with lifetime histories of SUDs had higher Abuse Scale scores and were more likely to score in the Elevated range (as determined by clinically significant cutoff scores) than parents without such histories. No differences were found between parents with current diagnoses of SUD and those with past (but not current) histories of SUD. Fathers and mothers with a partner who had a history of SUD were more likely to score in the Elevated range, regardless of their own SUD histories. Separate regression models revealed that, for both fathers and mothers, emotional dysregulation (positive and negative affectivity) predicted Abuse Scale scores. Additional contributors to Abuse Scale scores were SUD status in fathers, and lack of involvement with the child in mothers. CONCLUSIONS: History of SUDs in both fathers and mothers increases abuse potential. Contributors to abuse potential differed in fathers and mothers, underscoring the importance of examining parents separately in child maltreatment research.

Substance abuse and associated psychosocial problems among Argentina adolescents: sex heterogeneity and familial transmission.

OBJECTIVE: The goal of this investigation was to clarify the effects of sex and familial transmission in the psychosocial concomitants of substance abuse problems among adolescents. METHOD: Male (n = 956) and female (n = 303) adolescents in school, and male adolescents in a drug treatment program (n = 51) in Buenos Aires Province, Argentina were administered a translated version of the Drug Use Screening Inventory. Use of substances, familial substance abuse and associations between psychosocial problem domains and substance abuse problems were examined. RESULTS: Sex heterogeneity was broadly observed in terms of both substance abuse and psychosocial problems. Female adolescents in the school-based sample were found to generally report higher levels of psychosocial problems and greater use of minor tranquillizers than school boys or boys in treatment for substance abuse. Conduct deviancy was associated with substance abuse problems only in males, while health problems were associated only in females. However, among all youth, substance abuse problems were found to be associated with older age, greater social competency, problems in school performance, and involvement with deviant peers. Familial substance abuse was associated with substance abuse problems among all adolescents, however, the pattern of associations with other psychosocial problems differed between males and females. CONCLUSIONS: Sex heterogeneity was found in the associations between psychosocial problems, adolescent substance abuse, and familial substance abuse. Furthermore, the results are consistent with a syndrome of problem behaviors.

Increasing treatment adherence among outpatients with depression and cocaine dependence: results of a pilot study.

OBJECTIVE: This pilot study examined the effect of a modified motivational therapy intervention on outpatient treatment adherence and completion for patients with comorbid depressive disorder and cocaine dependence. METHOD: Depressed cocaine patients, stabilized with antidepressant medications on an inpatient psychiatric unit, were consecutively assigned on discharge to motivational therapy (N = 11) or treatment-as-usual (N = 12) during the first month of outpatient care. Patients were compared on treatment adherence and completion and on 1-year rehospitalization rates. RESULTS: Motivational therapy patients attended significantly more treatment sessions during month 1, completed 30 and 90 days of outpatient care at higher rates, and experienced fewer psychiatric rehospitalizations and days in the hospital during the first year from entry into outpatient treatment. CONCLUSIONS: An outpatient program combining individual and group motivational therapy sessions holds promise for improving treatment adherence and completion among depressed patients with cocaine dependence.

Early adolescent gateway drug use in sons of fathers with substance use disorders.

This study determined the relevance of preadolescent psychopathology and substance use for predicting early adolescent alcohol and cannabis involvement in boys of fathers with and without substance use disorders (SUD). Fathers of preadolescent boys (ages 10 through 12 years) were recruited to represent families of boys with paternal SUD (High Risk or HR: N = 102) and boys without paternal SUD (Low Average Risk or LAR: n = 166). These boys and a parental informant participated in semistructured diagnostic interviews at baseline and 2-year follow-up assessments (ages 12 through 14 years). Preadolescent tobacco experimentation and early adolescent regular alcohol use were more prevalent in HR than in LAR subjects. Logistic regression analyses were utilized to develop prediction equations. The presence of oppositional defiant disorder and the absence of anxiety disorders predicted preadolescent tobacco use. Preadolescent conduct disorder predicted early adolescent regular alcohol use. Preadolescent tobacco use and conduct disorder were highly predictive of early adolescent cannabis use, achieving 100% sensitivity with 76% specificity. Children with tobacco use prior to adolescence, as well as those with disruptive behavior disorders, may be important to target for interventions to prevent cannabis use.

Naltrexone utility in depressed alcoholics.

The aim of this open-label pilot study was to evaluate the utility of naltrexone (50 mg per day) in decreasing alcohol use and to examine its impact on depressive symptoms among depressed alcoholics who have failed to abstain from alcohol use despite treatment with a selective serotonin reuptake inhibitor (SSRI). Fourteen ambulatory care patients, aged 18 to 65 years, with DSM-III-R comorbid diagnoses of alcohol dependence and major depressive disorder, who failed to abstain despite treatment with an antidepressant medication were enrolled in the study. Patients were followed for 12 weeks with weekly assessment of drinking behavior, depressive symptoms, functioning, alcohol craving, and side effects. The results of this study indicated a significant decrease in alcohol use and in urges to drink alcohol in the presence of the usual triggers. There was also a trend suggesting improvement in depressive symptoms and overall functioning. Naltrexone was well tolerated, with mild side effects reported at the onset of treatment.

Drug use problem awareness and treatment readiness in dual-diagnosis patients.

Problem awareness and treatment readiness are factors that influence treatment-seeking behavior, and thus, morbidity and outcome. The authors elucidated patterns of problem awareness and treatment readiness among hospitalized dually diagnosed patients by administering the Problem Awareness and Readiness for Treatment subscales of the Alcohol Use Inventory to 67 psychiatric inpatients with comorbid substance-related disorders and using a multivariate model approach to data analysis. The results suggested differential and interactive effects of gender, ethnicity, voluntary admission status, and a diagnosis of major depression (MDD) on drug abuse problem awareness and treatment readiness. Female gender, voluntary admission status, and a comorbid diagnosis of MDD were associated with increased awareness and readiness for treatment.

Adolescent versus adult onset and the development of substance use disorders in males.

This study examines the influence of adolescent age of onset on the development of substance use disorders (SUD) by comparing adult males (n = 181) with SUD categorized into adolescent-onset, early-adult onset and late-adult onset groups on patterns of substance use and related disorders, time course of the development of substance dependence and rates of comorbid mental disorders. A sample of male adolescents (n = 81) with SUD was also included as a comparison group. The subjects were recruited from intervention programs in the community and participated in semistructured interviews with diagnoses determined by the best estimate method. Adolescent-onset adults, compared with other adult-onset groups, had higher lifetime rates of cannabis and hallucinogen use disorders, shorter times from first exposure to dependence, shorter times between the development of their first and second dependence diagnoses and higher rates of disruptive behavior disorders and major depression. Adolescents were similar to adolescent-onset adults. While the findings must be interpreted in light of methodological limitations, these results suggest that adolescent-onset SUD is a distinct subtype involving different substances and more rapid development than adult-onset SUD.

Behavioral self-regulation: correlates and 2 year follow-ups for boys at risk for substance abuse.

This investigation demonstrated the heuristic construct of behavioral self-regulation (BSR) as a salient component of the liability to substance abuse. Three dimensions of childhood behaviour were employed to create a dimensional model of BSR: inattention, impulsivity/hyperactivity and aggressivity. Multiple measures and multiple informants were employed to develop indices of the three traits in a sample of 10-12 year old sons of substance abusing fathers (high risk (HR); n = 180) and normal controls (low average risk (LAR); n = 200). Informants included mothers, boys and their teachers. The results confirmed the presence of a first-order latent trait of BSR. HR boys had significantly higher scores on BSR than LAR boys. Concurrent validity of the BSR trait scores was supported by significant associations with measures of family dysfunction, deviant peer affiliations and poor school performance. These latter problems are commonly prodromal to substance abuse. Predictive validity of the BSR trait baseline scores (age 10-12 years) was supported at 2 year follow-up by significant associations of BSR scores with magnitude of deviant peer affiliations; trends toward significance were found for family dysfunction and poor school performance. Taken together, these results confirm and extend previous findings which indicate that poor BSR is prodromal to substance abuse.

The Drug Use Screening Inventory for adults: psychometric structure and discriminative sensitivity.

The psychometric structure and characteristics of the adult version of the Drug Use Screening Inventory were examined in alcohol and drug abusers (n = 119) and normal controls (n = 119). It was found that each of the 10 DUSI domains is unidimensional. Inter-item, split half and internal reliability ranged from good to excellent. A score of 4 or higher on the Substance Use Domain correctly classified 80% of the substance abusers whereas a score of 3 or less accurately detected 100% of the normal control subjects. These results demonstrate that the DUSI is a practical and psychometrically sound screening instrument.

Multivariate typology of adolescents with alcohol use disorder.

Adolescent patients qualifying for a DSM-II-R diagnosis of alcohol use disorder were studied to determine whether a multidimensional schema could classify subjects into subgroups. The Drug Use Screening Inventory was administered to 151 subjects. To test the concurrent validity of the subtypes, subjects also received a structured diagnostic psychiatric evaluation along with measures of personality, academic achievement, and drinking behavior. Two clusters were identified for each gender. Differences between clusters were reflected primarily on indicators of severity of disorder. Young women were more inclined toward affective disturbances, whereas conduct disorder was the most frequent disorder in young men. This study underscores the heterogeneity of the adolescent population qualifying for a diagnosis of alcohol use disorder. The differential pattern of alcohol involvement and comorbid psychopathology within clusters and between genders demonstrates the need for interventions tailored to specific clinical presentation.