Robert Milin

A Consecutive Series of Treated Affected Offspring of Parents With Bipolar Disorder: Is Response Associated With the Clinical Profile?

Objective: In adults with established bipolar disorder (BD), differential response to mood stabilizers has been associated with the clinical profile. Long-term treatment studies of youth with BD are lacking. This paper provides longitudinal observations of response to mood stabilizers early in the course of illness in youth with BD. Method: We report on 15 research patients who, as adolescents, met DSM-IV lifetime criteria for a bipolar spectrum disorder and required long-term treatment. These youths derived from families with one parent having BD whose course and long-term treatment response were determined in accordance with research criteria. The patients were offered lithium, and if they failed to respond or refused it, they were treated with either an anticonvulsant or an atypical antipsychotic. Using a validated scale, an independent rater retrospectively blindly scored the response to long-term treatment. Results: Those patients who stabilized on lithium derived from lithium-responsive families, whereas those who stabilized on an antipsychotic derived from lithium-nonresponsive families. The clinical course in the youths stabilized by lithium differed from that in the youths stabilized by an atypical antipsychotic. Conclusions: Our findings suggest that the clinical profile may help in selecting effective stabilizing treatment and that a proportion of youth can be stabilized on monotherapy. This is a small case series with nonrandom treatment assignment, and the findings should be considered tentative.

Prospective Assessment of Cannabis Withdrawal in Adolescents With Cannabis Dependence: A Pilot Study

OBJECTIVEnTo prospectively identify and assess withdrawal symptoms in adolescents with cannabis dependence.nnnMETHODnTwenty-one adolescents ages 13 to 19 years voluntarily entering residential and day/outpatient substance abuse programs, with cannabis dependence as their only current substance of dependence, were assessed using the Teen-Addiction Severity Index, Substance Use Survey, Cannabis Withdrawal Scale, and the Structured Clinical Interview for DSM-IV Childhood Diagnoses Substance Use Disorders Module. Weekly assessments continued for 4 weeks. Thirteen youths attained a minimum of 2 weeks of abstinence.nnnRESULTSnCannabis withdrawal symptoms were present in adolescents. Cannabis withdrawal was greatest in the first 2 weeks of abstinence with evidence that it continued well into week 3. Most withdrawal symptoms were endorsed with a high degree of frequency. Those symptoms endorsed with the greatest severity were restlessness, appetite change, and thoughts of and cravings for cannabis, with the highest ratings occurring in week 1. Over the course of the study, participants reported fewer symptoms with decreasing levels of severity. Youth ratings of overall severity of withdrawal were significantly and positively correlated with withdrawal symptoms of irritability (r = 0.56), depression (r = 0.56), twitches and shakes (r = 0.57), perspiring (r = 0.57), thoughts of (r = 0.86), and cravings for (r = 0.69) cannabis.nnnCONCLUSIONSnFindings support the presence of clinically significant cannabis withdrawal symptoms in adolescents with cannabis dependence seeking substance abuse treatment. This study also provides supporting evidence suggesting a vulnerability of adolescents to physiological cannabis dependence. The study supports the addition of cannabis withdrawal as a distinct entity for inclusion in DSM-V.

Sertraline Effects in Adolescent Major Depression and Dysthymia: A Six-Month Open Trial

This 6-month open-label study evaluated the efficacy, tolerability, and safety of sertraline in 21 adolescent psychiatric outpatients, ages 12 to 18 years, diagnosed with major depressive disorder (MDD, n = 13) or dysthymic disorder (DD, n = 8). Both groups showed clinically significant improvements on the Hamilton Depression Scale (HAM-D), Hamilton Anxiety Scale, and the Clinical Global Impression Scale-Severity (CGI-S). The MDD group showed maximal clinical response (based on the method of last observation carried forward) on the HAM-D and CGI at weeks 12 (76.9%) and 20 (76.9%), respectively. Response rates were maintained at week 24 with all six MDD study completers (100%) responding to treatment. The DD group achieved maximal response on the HAM-D (100%) and the CGI (75%) at week 6. Response rates in this group did not remain as elevated over time with two out of three (66.7%) DD study completers responding to treatment at week 24. Generally, sertraline was safe and well tolerated. Most adverse events were mild to moderate in severity and resolved with no action taken. Results suggest that sertraline may be efficacious in acute and continuation treatment of MDD in adolescents. DD patients showed evidence of clinical response and improvement, particularly in the acute treatment phase. Incorporating a longer evaluation period in the study of antidepressant therapy for adolescents with MDD and/or DD is emphasized.

Impact of a Mental Health Curriculum on Knowledge and Stigma Among High School Students: A Randomized Controlled Trial

OBJECTIVEnThis study evaluated the effectiveness of a school-based mental health literacy intervention for adolescents on knowledge and stigma.nnnMETHODnA total of 24 high schools and 534 students in the regional area of Ottawa, Ontario, Canada participated in this randomized controlled trial. Schools were randomly assigned to either the curriculum or control condition. The curriculum was integrated into the provinces grade 11 and 12 Healthy Living courses and was delivered by teachers. Changes in mental health knowledge and stigma were measured using pre- and posttest questionnaires. Descriptive analyses were conducted to provide sample characteristics, and multilevel modeling was used to examine study outcomes.nnnRESULTSnFor the curriculum condition, there was a significant change in stigma scores over time (pxa0= .001), with positive attitudes toward mental illness increasing from pre to post. There was also a significant change in knowledge scores over time (pxa0< .001), with knowledge scores increasing from pre to post. No significant changes in knowledge or stigma were found for participants in the control condition. A meaningful relationship was found whereby increases in knowledge significantly predicted increases in positive attitudes toward mental health (pxa0< .001).nnnCONCLUSIONnThis is the first large randomized controlled trial to demonstrate the effectiveness in mental health literacy of an integrated, manualized mental health educational resource for high school students on knowledge and stigma. Findings also support the applicability by teachers and suggest the potential for broad-based implementation of the educational curriculum in high schools. Replication and further studies are warranted. Clinical trial registration information-Impact of a Mental Health Curriculum for High School Students on Knowledge and Stigma; http://clinicaltrials.gov/; NCT02561780.

Neurocognitive functioning in the early stages of bipolar disorder: visual backward masking performance in high risk subjects.

IntroductionCognitive deficits, including deficits in early information processing, are associated with remitted bipolar disorder. The temporal relationship between these deficits and the clinical course is not known. The current study investigated whether or not deficits in early information processing were present before the onset and/or during the early stages of bipolar disorder.MethodsUnaffected and remitted high risk offspring of well-characterized bipolar parents completed a visual backward masking task. For comparison we included a cohort of unaffected offspring of well parents and a clinically referred group of remitted bipolar patients.ResultsThere was no evidence of a deficit in early information processing in well high risk subjects. As expected, the referred patient group had the highest error rates. After excluding the patients, interaction effect showed that the affected remitted high risk subjects performed differently in terms of error rates than unaffected high risk and control subjects. There were no significant differences in response times across study groups. Exploratory analyses revealed an association between a lifetime history of psychosis and increased errors on the task.ConclusionsThere was no evidence of a vulnerability in early information processing in offspring at risk for bipolar disorder. However, there were emergent changes in performance in the affected remitted high risk group. Psychosis appears to be an important clinical correlate associated with cognitive deficits. Mapping of the early course of bipolar disorder and associated changes in cognition has important implications for establishing critical periods for intervention.

Bipolar Disorder and the Onset of Substance Use Disorders in Adolescents: The Emerging Story

t was with great interest that I received the invitation to comment on adolescent substance I use disorder (SUD) findings from the leading longitudinal multisite study of children and adolescents with bipolar spectrum disorders (BPs), known as the Course and Outcome of Bipolar Youth (COBY) study. The group’s initial article on SUD in adolescents with BP from the COBY sample found a lifetime SUD rate of 16% on admission to the study, a frequency of occurrence somewhat lower than one would expect. However, SUD was associated with an increased likelihood of having a history of adverse psychological events, including suicide attempts. In this issue of the Journal, Goldstein et al. examine the development of first-onset SUD in 167 adolescents with BP from the COBY study who did not present with comorbid SUD. These adolescents with BP were prospectively evaluated in follow-up interviews over the course of on average 4 years before entering into adulthood. Approximately one third (32.3%) of the adolescents developed SUD over the course of followup, a substantive number, with the average age of onset of SUD being 18 years. Cannabis and alcohol use disorders represented the vast majority of SUD cases. In their study, the investigators identified some (6) predictive factors associated with an increased risk of developing a SUD, the most clinically relevant predictors being recreational use of alcohol, lifetime history of oppositionaldefiant disorder, and a family history of SUD. The risk of developing a SUD increased significantly with the number of predictive factors. Thus, 54.7% of adolescents with 3 or more predictive factors developed a SUD in contrast to only 14% of adolescents with 2 or fewer predictive factors.