Susan C. Sonne

Cocaine Dependence with and without Post-traumatic Stress Disorder: A Comparison of Substance Use, Trauma History and Psychiatric Comorbidity

This study examined the relationship between substance use, trauma history, post-traumatic stress disorder (PTSD), and psychiatric comorbidity in a treatment seeking sample of cocaine dependent individuals (N = 91). Structured clinical interviews revealed that 42.9% of the sample met DSM-III-R criteria for lifetime PTSD. Comparisons between individuals with and without lifetime PTSD revealed that individuals with PTSD had significantly higher rates of exposure to traumatic events, earlier age of first assault, more severe symptomatology, and higher rates of Axis I and Axis II diagnoses. The results illustrate a high incidence of PTSD among cocaine dependent individuals. Routine assessment of trauma history and PTSD may assist in the identification of a subgroup of cocaine users in need of special prevention and treatment efforts.

Symptom Improvement in Co-Occurring PTSD and Alcohol Dependence

This study investigated the temporal course of improvement in PTSD and alcohol dependence symptoms among individuals participating in a 12-week outpatient treatment study. Participants were 94 individuals with comorbid PTSD and alcohol dependence enrolled in a double-blind, placebo-controlled medication trial. Outcome measures included PTSD symptoms (as measured by the Clinician Administered PTSD Scale, Impact of Events Scale, and Civilian Mississippi Scale for PTSD) and alcohol use severity (as measured by the Time Line Follow Back). Study completion rates were significantly higher for individuals who demonstrated improvement in both disorders. Improvements in PTSD had a greater impact on improvement in alcohol dependence symptoms than the reciprocal relationship. Improvement in hyperarousal PTSD symptoms, in particular, was related to substantially improved alcohol use. Examination of the temporal course of symptom improvement revealed that alcohol symptoms tended to start improving either before or in conjunction with PTSD symptoms. Although preliminary in nature, these findings suggest that co-occurring PTSD symptoms may have a strong impact on alcohol dependence treatment outcome, and that PTSD treatment may be important to optimizing outcomes for patients with comorbid PTSD and alcohol dependence.

Sertraline in the treatment of co-occurring alcohol dependence and posttraumatic stress disorder

BACKGROUND Posttraumatic stress disorder (PTSD) frequently co-occurs with alcohol use disorders. This study investigated the use of sertraline, a serotonin reuptake inhibitor, in treating co-occurring symptoms of alcohol dependence and PTSD. METHODS A total of 94 individuals with current alcohol dependence and PTSD were randomly assigned to receive sertraline (150 mg/day) or placebo for 12 weeks. Post hoc cluster analysis of baseline characteristics was used to define subgroups of participants. RESULTS There was a significant decrease in alcohol use during the trial in both the sertraline and the placebo groups. Cluster analysis revealed significant medication group by cluster interactions for alcohol-related outcomes. Sertraline-treated participants with less severe alcohol dependence and early-onset PTSD had significantly fewer drinks per drinking day (p < 0.001). For participants with more severe alcohol dependence and later onset PTSD, the placebo group had significantly greater decreases in drinks per drinking day (p < 0.01) and average number of drinks consumed per day (p < 0.05). CONCLUSIONS There may be subtypes of alcohol-dependent individuals who respond differently to serotonin reuptake inhibitor treatment. Further investigation of differential responders may lead to improvements in the pharmacological treatment of co-occurring alcohol dependence and PTSD.

Genomewide Linkage Scan for Opioid Dependence and Related Traits

Risk of opioid dependence is genetically influenced. We recruited a sample of 393 small nuclear families (including 250 full-sib and 46 half-sib pairs), each with at least one individual with opioid dependence. Subjects underwent a detailed evaluation of substance dependence-related traits. As planned a priori to reduce heterogeneity, we used cluster analytic methods to identify opioid dependence-related symptom clusters, which were shown to be heritable. We then completed a genomewide linkage scan (with 409 markers) for the opioid-dependence diagnosis and for the two cluster-defined phenotypes represented by >250 families: the heavy-opioid-use cluster and the non-opioid-use cluster. Further exploratory analyses were completed for the other cluster-defined phenotypes. The statistically strongest results were seen with the cluster-defined traits. For the heavy-opioid-use cluster, we observed a LOD score of 3.06 on chromosome 17 (empirical pointwise P = .0002) for European American (EA) and African American (AA) subjects combined, and, for the non-opioid-use cluster, we observed a LOD score of 3.46 elsewhere on chromosome 17 (empirical pointwise P = .00002, uncorrected for multiple traits studied) for EA subjects only. We also identified a possible linkage (LOD score 2.43) of opioid dependence with chromosome 2 markers for the AA subjects. These results are an initial step in identifying genes for opioid dependence on the basis of a genomewide investigation (i.e., a study not conditioned on prior physiological candidate-gene hypotheses).

SUBSTANCE ABUSE AND BIPOLAR COMORBIDITY

Bipolar disorder and substance abuse commonly co-occur. In fact, as many as 50% of individuals with bipolar disorder have been found to have a lifetime history of substance abuse or dependence. This article discusses the very important comorbidity of bipolar disorder as it is complicated by substance abuse, focusing on the prevalence, course, diagnostic considerations and treatment.

Venlafaxine: A Structurally Unique and Novel Antidepressant

Objective: To introduce the new antidepressant venlafaxine. Basic pharmacokinetic data and clinical trials are reviewed, as well as adverse reactions, drug interactions, dosing guidelines, and therapeutic considerations. The article also discusses several pharmacotherapy issues and how venlafaxine compares with other available antidepressants. Data Sources: A MEDLINE search was used to identify pertinent literature, including reviews. Study Selection: As this is a relatively new agent, all available clinical trials were reviewed. Data Extraction: All clinical trials that were available prior to submission for publication were reviewed. Preliminary trials and unpublished reports were not reviewed. Data Synthesis: Venlafaxine hydrochloride is a structurally novel agent that has recently been approved in the US for the treatment of depression. This unique antidepressant blocks neuronal reuptake of norepinephrine, serotonin, and, to a lesser extent, dopamine. Venlafaxine and its major active metabolite, O—desmethylvenlafaxine, exhibit linear kinetics with an elimination half-life of 5 and 11 hours, respectively. Venlafaxine has been evaluated in 7 clinical trials for the treatment of depression. These have consisted of 2 open trials, 3 double-blind, placebo-controlled trials, and 2 double-blind trials where venlafaxine was compared with trazodone and imipramine. All 7 trials have established efficacy for venlafaxine using standard psychiatric rating scales to measure change of depressive symptoms. The usual daily dosage ranges from 75 to 225 mg/d in 2 to 3 divided doses, with a maximum daily dosage of 375 mg/d. The drugs adverse effect profile differs somewhat from other more specific serotonin reuptake inhibitors in that it appears to cause dry mouth, somnolence, and elevated blood pressure as well as nausea, headache, and dizziness. Conclusions: Although venlafaxine has recently become available for use as an antidepressant in the US, few clinical trials have been conducted to help the practitioner evaluate its place in the treatment of depression. There are no comparative trials of venlafaxine with the serotonin specific reuptake inhibitor antidepressants, which are rapidly becoming the newest comparative standard. The clinical place for venlafaxine in the treatment of depression has yet to be determined.

Features of cocaine dependence with concurrent alcohol abuse

In order to assess differences between cocaine dependence alone and cocaine dependence complicated by alcohol abuse, 34 subjects who met DSM-III-R criteria for alcohol abuse and cocaine dependence (COC-ETOH group) were compared with 39 subjects who met criteria for cocaine dependence only (COC-only group) with regard to demographics, substance use, and psychopathology. There were no differences between groups in age, race, employment or socio-economic status. The baseline depression and global severity scores in the COC-ETOH group were significantly higher than in the COC-only group. The COC-ETOH group was significantly more likely to experience a paranoid psychosis with cocaine use and significantly more likely to have abused additional substances in the month prior to study entry. The COC-ETOH group also attended significantly fewer medication management sessions during the 12-week trial. There were no differences between groups in the type or frequency of Axis 1 or Axis II disorders.

Comparative Profiles Of Women With Ptsd And Comorbid Cocaine Or Alcohol Dependence

This study examined differences in substance abuse severity, trauma history, posttraumatic stress disorder (PTSD) symptomatology and psychiatric comorbidity among treatment-seeking women (N=74) with PTSD and either comorbid cocaine or alcohol dependence. Women in the cocaine/PTSD group, compared with the alcohol/PTSD group, demonstrated greater occupational impairment (e.g., greater severity on the employment subscale of the Addiction Severity Index, less monthly income, fewer days worked in past month), more legal problems (e.g., greater number of months incarcerated and arrests for prostitution), and greater social impairment (e.g., fewer number of close friends, less likely to be married). Women in the alcohol/PTSD group evidenced higher rates of exposure to serious accidents, other situations involving serious injury, and other extraordinarily stressful life events. Rates of major depression and social phobia were higher among the alcohol/PTSD group than the cocaine/PTSD group. Women in the alcohol/PTSD group scored higher on the CAPS avoidance, hyperarousal, and total subscale scores. The current findings enhance our understanding of the substance-specific profiles of women with PTSD and comorbid substance use disorders and may have important implications for the design of dual-diagnosis interventions.

Carbamazepine in the treatment of cocaine dependence: subtyping by affective disorder.

Studies investigating carbamazepine (CBZ) in the treatment of cocaine dependence have been inconsistent. In this study, cocaine-dependent individuals with (n = 57) and without (n = 82) affective disorder were compared in a 12-week, double-blind, placebo-controlled trial. Urine drug screens (UDS) and self-report of drug use were collected weekly. Affective symptoms were measured monthly. Subjects receiving CBZ attended more medication sessions (p = .03). The CBZ-treated affective group had a trend toward fewer cocaine-positive UDS (p = .08) and a significantly longer time to first cocaine use (p = .06). CBZ treatment did not have any impact on cocaine use in individuals without affective disorders.

Practical considerations for estimating clinical trial accrual periods: application to a multi-center effectiveness study

BackgroundAdequate participant recruitment is vital to the conduct of a clinical trial. Projected recruitment rates are often over-estimated, and the time to recruit the target population (accrual period) is often under-estimated.MethodsThis report illustrates three approaches to estimating the accrual period and applies the methods to a multi-center, randomized, placebo controlled trial undergoing development.ResultsIncorporating known sources of accrual variation can yield a more justified estimate of the accrual period. Simulation studies can be incorporated into a clinical trials planning phase to provide estimates for key accrual summaries including the mean and standard deviation of the accrual period.ConclusionThe accrual period of a clinical trial should be carefully considered, and the allocation of sufficient time for participant recruitment is a fundamental aspect of planning a clinical trial.