Study Investigates Long-Term Course of ADHD
A recent follow-up of the Multisite Treatment Study of Children with ADHD (MTA) study investigated the long-term course of ADHD and the impact of short-term treatment on long-term outcomes. A decade ago, children with ADHD were randomly assigned to one of four treatments for 14 months: stimulant medication, behavioral treatment, combined medication and behavioral treatment, or usual care in the community. At the endpoint, medication and combined treatment showed significantly greater improvement than behavioral treatment or usual care, though all groups showed improvement over the initial study period (MTA Cooperative Group. Arch Gen Psychiatry 1999;56:1073-1086), After 14 months, all participants’ families were free to seek treatment in the community as they deemed appropriate, and researchers monitored the children’s ADHD symptoms periodically. By the end of three years, the initial advantage of medication treatment over behavioral treatment disappeared (Jensen PS et al., J Am Acad Child Adolesc Psychiatry 2007;46:989-1002). The present study, which is the eight-year follow-up of the same patients, again found that having been in one of the medication groups for the initial study did not influence long-term outcomes. In general, children in the MTA study continued to lag behind non-ADHD children on academic and mental health measures (Molina SG et al., 2008 J Am Acad Child Adolesc Psychiatry 2009;48:484-500).
TCPR’s Take: While some commentators believe these long term data indicate that stimulants have little long term efficacy, such a conclusion does not necessarily follow from the data. Since patients’ treatment was no longer randomized after 14 months, over the ensuing years some children originally assigned to medication discontinued stimulants, while some originally assigned to therapy started medication. Unfortunately, the long-term physical impact of stimulants has received little study, though three year follow-up of MTA participants found that newly medicated patients grew an average 0.9 inches less and gained 5.95 fewer pounds than the non-medicated children in the study (Swanson JM et al., J Am Acad Child Adolesc Psychiatry 2007;46:1015-1027).
Predictors of Suicidal Behavior in Adolescent Treatment-Resistant Depression
Researchers assessed predictors of suicidal events and non-suicidal self-harm in a group of 334 moderately to severely depressed adolescents (ages 12-18) who had not responded to at least eight weeks of SSRI treatment. Participants were switched to one of four treatments: a different SSRI, venlafaxine, a different SSRI plus cognitive-behavior therapy (CBT), or venlafaxine plus CBT. Initially, the researchers examined suicidal events and non-suicidal self-harm through spontaneous reports from participants. Halfway through the study, because of concerns raised by the FDA about antidepressants and suicidality, researchers switched to using a more systematic method of assessing suicidality and self-harm, asking specific questions about suicidal intent and behavior on a weekly basis. (Not surprisingly, researchers detected that participants reported significantly more suicidal events (20.9% vs. 8.8%) and non-suicidal self-injury events (17.6% vs. 2.2%) when the more systematic method of evaluating suicidality was utilized.) Generally, there were no significant differences between treatment groups; however, patients whose baseline suicidal ideation was higher than average were significantly more likely to experience a suicidal event on venlafaxine during the study than patients receiving SSRIs (37.2% vs. 23.3%). Regardless of treatment, patients with any of three characteristics – a history of non-suicidal self-injury, severe drug use, or serious family conflict – were more likely to experience suicidal events during the study (Brent DA et al., Am J Psychiatry 2009;166:418-426).
TCPR’s Take: There is a lot going on in this study. Regarding treatment options for adolescents, the study suggests that venlafaxine may be riskier for adolescents than SSRIs, although the numbers are small. What is perhaps more interesting for clinical practice, though, are some of the secondary findings. The study points to three significant factors that should be carefully assessed in adolescent patients: history of suicidal behavior, current drug use, and level of family conflict. The change in the method of evaluating suicidality was also noteworthy. While systematic monitoring revealed a much higher rate of suicidal behavior and of self-harm than did spontaneous report, both methods caught about the same number of serious events (defined as those that led to hospitalization, or that were life-threatening or disabling). Nevertheless, one of the lessons from this study is: Don’t wait for your patients to volunteer information on suicidal ideation – instead, ask explicitly about this at each visit.
Discontinuing Antipsychotics May Decrease Mortality Risk in Dementia
In a 2005 public health advisory, the FDA warned that antipsychotics appear to increase the rate of mortality in elderly patients with dementia. The implication is that we should discontinue such agents in this population when possible. But does this actually decrease the mortality risk? A recent randomized trial attempted to answer this question. In this study, 165 patients with dementia who were already taking antipsychotics were randomly assigned to either continue their antipsychotic regimen or switch to placebo for one year. During that year, more of the patients taking an antipsychotic died of any cause (30%) than did those taking placebo (23%). After a year, the randomized treatments were discontinued and patients were placed on treatment as deemed appropriate by their physicians. When the original two groups were compared after three and a half years (42 months), there were significantly more survivors from the placebo group (53%) than from the antipsychotic group (26%) (Ballard C et al., 2009 Lancet Neurol 2009;8:151-157).
TCPR’s Take: The researchers did not track which medications were received by patients after the initial 12-month trial, so some of the patients in the placebo group likely restarted antipsychotics, while some patients who initially took antipsychotics may have discontinued them. That said, the group receiving antipsychotics during the 12-month trial quite likely had a greater cumulative exposure to the drugs than did the placebo group. Prior research has suggested minimal benefits and increased risk of mortality for antipsychotics in treating dementia (Schneider et al., 2006 Am J Geriatr Psychiatry;14:191-210). The bottom line is that we should minimize demented patients’ exposure to antipsychotic medications.