Ihsan M. Salloum

Modafinil for the treatment of cocaine dependence

AIM Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo. METHODS This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Six outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, having a diagnosis of cocaine dependence; 72 participants were randomized to placebo, 69 to modafinil 200mg, and 69 to modafinil 400mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy weekly. The primary outcome measure was the weekly percentage of cocaine non-use days. RESULTS The GEE regression analysis showed that for the total sample, there was no significant difference between either modafinil group and placebo in the change in average weekly percent of cocaine non-use days over the 12-week treatment period (p>0.79). However, two secondary outcomes showed significant effects by modafinil 200mg: the maximum number of consecutive non-use days for cocaine (p=0.02), and a reduction in craving (p=0.04). Also, a post hoc analysis showed a significant effect of modafinil that increased the weekly percentage of non-use days in the subgroup of those cocaine patients who did not have a history of alcohol dependence (p<0.02). CONCLUSIONS These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing cocaine craving.

A multi-site dose ranging study of nalmefene in the treatment of alcohol dependence

Abstract: The opiate antagonist nalmefene has been shown in 2 single-site studies to reduce alcohol consumption and relapse drinking in alcohol-dependent individuals. This safety and preliminary multisite efficacy study evaluated 3 doses of nalmefene (5, 20, or 40 mg) in a double-blind comparison to placebo over a 12-week treatment period in 270 recently abstinent outpatient alcohol-dependent individuals. Participants concomitantly received 4 sessions of a motivational enhancement therapy (with a medication compliance component) delivered from trained counselors. Although more subjects in the active medication groups terminated the study early secondary to adverse events, the rates did not differ significantly from that of placebo. The 20-mg/d group experienced more insomnia, dizziness, and confusion, while the 5-mg group also had more dizziness and the 40-mg group had more nausea than the placebo group. Most of these symptoms were mild and improved over time. Although all subjects had a reduction in heavy drinking days, craving, γ-glutamyl transferase, and carbohydrate-deficient transferrin concentrations over the course of the study, there was no difference between the active medication and placebo groups on these measures. The time to first heavy drinking day was also not significantly different between the placebo and the active treatment groups. This relatively small multisite trial showed that nalmefene was reasonably well tolerated in recently abstinent alcoholics. However, possibly because of variation among the sites or the comparatively small sample size, there was no evidence of superior efficacy outcomes with nalmefene treatment.

Rapid relapse generally follows treatment for substance use disorders among adolescents.

This prospective study involved 59 adolescents with drug and alcohol disorders who had just completed outpatient treatment. They participated in a comprehensive baseline assessment, and then participated in monthly telephone assessments of substance use and reasons for use. Despite their recent treatment, two-thirds (66%) of the participants in this study had relapsed to drug use within 6 months. The median time to drug relapse was only 54 days (+/-14 days), or slightly less than 2 months. The three most commonly given reasons for relapse were social pressure, withdrawal, and negative affect. These findings provide a first confirmation of the results of S.A. Brown [Recovery patterns in adolescent substance abuse. (1993). In J. S. Baer, G. A. Marlatt, & R. J. McMahon (Eds.), Addictive behaviors across the life span (pp. 160-183). London: SAGE.] in showing that most adolescents relapse quickly following treatment for substance use disorders.

Impact of substance use disorders on recovery from episodes of depression in bipolar disorder patients: prospective data from the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

OBJECTIVE Bipolar disorder is highly comorbid with substance use disorders, and this comorbidity may be associated with a more severe course of illness, but the impact of comorbid substance abuse on recovery from major depressive episodes in these patients has not been adequately examined. The authors hypothesized that comorbid drug and alcohol use disorders would be associated with longer time to recovery in patients with bipolar disorder. METHOD Subjects (N=3,750) with bipolar I or bipolar II disorder enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were followed prospectively for up to 2 years. Prospectively observed depressive episodes were identified for this analysis. Subjects with a past or current drug or alcohol use disorder were compared with those with no history of drug or alcohol use disorders on time to recovery from depression and time until switch to a manic, hypomanic, or mixed episode. RESULTS During follow up, 2,154 subjects developed a new-onset major depressive episode; of these, 457 subjects switched to a manic, hypomanic, or mixed episode prior to recovery. Past or current substance use disorder did not predict time to recovery from a depressive episode relative to no substance use comorbidity. However, those with current or past substance use disorder were more likely to experience switch from depression directly to a manic, hypomanic, or mixed state. CONCLUSIONS Current or past substance use disorders were not associated with longer time to recovery from depression but may contribute to greater risk of switch into manic, mixed, or hypomanic states. The mechanism conferring this increased risk merits further study.

Alcohol and psychiatric comorbidity.

Comorbid psychiatric disorders and drug use disorders (DUDs) are common among alcoholics (Regier, Farmer, Rae, Locke, Keith, Judd, & Goodwin, 1990; Kessler, McGonagle, Zhao, Nelson, Hughes, Eshleman, Wittchen, & Kendler, 1994). These comorbid disorders often predict a shorter time to relapse of alcoholism (Greenfield, Weiss, Muenz, Vagge, Kelly, Bello, & Michael, 1998). However, despite the prevalence and the adverse effects of this comorbidity, few controlled treatment studies have been conducted involving this dual diagnosis population (Litten & Allen, 1999). To date, most of these few studies of alcoholics with comorbid disorders have been restricted to studies of alcoholics with either comorbid major depression or comorbid anxiety disorders (Litten & Allen, 1995). The results of these trials suggest efficacy for SSRI antidepressants and tricyclic antidepressants for treating alcoholics with comorbid major depression and suggest efficacy for buspirone for treating alcoholics with comorbid anxiety disorders (Mason, Kocsis, Ritvo, & Cutler, 1996; Cornelius, Salloum, Ehler, Jarrett, Cornelius, Perel, Thase, & Black, 1997; Kranzler, Burleson, Del Boca, Babor, Korner, Brown, & Bohn, 1994). However, controlled treatment studies involving alcoholics with other comorbid disorders are almost totally lacking. Consequently, to date, no empirically proven treatment exists for most of these comorbid disorders.

General-Medical Conditions in Older Patients With Serious Mental Illness

OBJECTIVE The burden of medical comorbidities was compared between older (> or =60 years) and younger patients with serious mental illness. METHODS Patients (N=8,083) diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder in 2001 were identified from VA facilities in the mid-Atlantic region. Medical comorbidities were identified by an ICD-9-based clinical classification algorithm. RESULTS Older, versus younger, patients were more likely to be diagnosed with cardiovascular or pulmonary conditions, and less likely to be diagnosed with substance-use disorders or hepatic conditions. CONCLUSIONS More aggressive detection and management of general-medical comorbidities in older patients with serious mental illness is paramount.

Person-Centred Integrative Diagnosis: Conceptual Bases and Structural Model

Objectives: To review the conceptual bases of Person-centred Integrative Diagnosis (PID) as a component and contributor to person-centred psychiatry and medicine and to outline its design and development. Method: An analysis was conducted of the historical roots of person-centred psychiatry and medicine, tracing them back to ancient Eastern and Western civilizations, to the vicissitudes of modern medicine, to recent clinical and conceptual developments, and to emerging efforts to reprioritize medicine from disease to patient to person in collaboration with the World Medical Association, the World Health Organization, the World Organization of Family Doctors, the World Federation for Mental Health, and numerous other global health entities, and with the coordinating support of the International Network for Person-centered Medicine. Results: One of the prominent endeavours within the broad paradigmatic health development outlined above is the design of PID. This diagnostic model articulates science and humanism to obtain a diagnosis of the person (of the totality of the persons health, both ill and positive aspects), by the person (with clinicians extending themselves as full human beings), for the person (assisting the fulfillment of the persons health aspirations and life project), and with the person (in respectful and empowering relationship with the person who consults). This broader and deeper notion of diagnosis goes beyond the more restricted concepts of nosological and differential diagnoses. The proposed PID model is defined by 3 keys: broad informational domains, covering both ill health and positive health along 3 levels: health status, experience of health, and contributors to health; pluralistic descriptive procedures (categories, dimensions and narratives); and evaluative partnerships among clinicians, patients, and families. An unfolding research program is focused on the construction of a practical guide and its evaluation, followed by efforts to facilitate clinical implementation and training. Conclusions: PID is aimed at appraising overall health through pluralistic descriptions and evaluative partnerships, and leading through a research program to more effective, integrative, and person-centred health care.

Racial effects on the clinical presentation of alcoholics at a psychiatric hospital.

Little is known about the effects of age on the clinical presentation of alcoholism in various treatment settings, despite the clinical importance of this factor. This study evaluates the effects of age on the clinical profile of 604 alcoholics who presented for initial evaluation and treatment at a psychiatric hospital. Young alcoholics displayed the most prominent substance use, antisocial behavior, depressive symptoms (including suicidality), and impulsivity. Early middle-aged alcoholics displayed the highest levels of drinking. Elderly alcoholics displayed the highest levels of cognitive dysfunction, although some level of cognitive dysfunction was present among even the youngest alcoholics. These findings confirm and clarify the effects of age on the clinical profile of alcoholics presenting for initial evaluation at a psychiatric hospital.

Fluoxetine in adolescents with major depression and an alcohol use disorder: An open-label trial

Recently, a first placebo-controlled study of an selective serotonin reuptake inhibitor (SSRI) medication was conducted among a sample of adolescents with major depression by Emslie et al. [Arch. Gen. Psychiatry 54 (1997) 1031.]. That study demonstrated efficacy for fluoxetine vs. placebo for treating adolescents with major depression. However, to date, no studies have been conducted to assess the efficacy of fluoxetine or any other SSRI medication in adolescents with major depression in combination with an alcohol use disorder (AUD). In this study, the authors investigated whether fluoxetine decreases the depressive symptoms and the drinking of adolescents with comorbid major depression and an AUD. The authors conducted a 12-week open-label study of fluoxetine (20 mg) in 13 adolescents with current comorbid major depression and an AUD. A significant within-group decrease (improvement) was found for both depressive symptoms and drinking during the course of the study. The fluoxetine was well tolerated during the study. These data suggest promise for fluoxetine for decreasing both the depressive symptoms and the drinking of adolescents with comorbid major depression and an AUD.

Treatment adherence and illness insight in veterans with bipolar disorder.

Insight into the perceived value of psychotherapy and pharmacological treatment may improve adherence to medication regimens among patients with bipolar disorder, because patients are more likely to take medication they believe will make them better. We conducted a cross-sectional survey of patients recruited into the Continuous Improvement for Veterans in Care—Mood Disorders (CIVIC-MD; July 2004–July 2006), assessing therapeutic insight and 2 measures of medication adherence: the Morisky scale of intrapersonal barriers and missing any doses the previous 4 days. Among 435 patients with bipolar disorder, 27% had poor adherence based on missed dose and 46% had poor adherence based on the Morisky. In multivariable models, greater insight into medication was negatively associated with both measures of poor adherence. Odds of poor adherence increased for women, African Americans, mania, and hazardous drinking. The association of mutable factors—hazardous drinking, manic symptoms, and insight—could represent an opportunity to improve adherence.