Jeff Bostic, M.D., E.d.D.
Director of School Psychiatry, Massachusetts General Hospital
Assistant Clinical Professor of Psychiatry, Harvard Medical School
TCR: Dr. Bostic, what are your clinical and research responsibilities? Dr. Bostic: I work in five different school districts, doing school consultations, helping the mental health and teaching staff deal more effectively with kids. I'm involved with the STAART grant funded by NIMH which is a study of children with autism at 8 sites throughout the country. We're going to do a citalopram study of autistic kids which will begin in December of this year. I also have a private practice in which I see adolescents and young adults, primarily with depression, and increasingly PDD spectrum disorders.
TCR: So what kind of advice would you give those of us who are primarily adult psychiatrists but who are called upon increasingly to see kids for depression, because there is such a shortage of child psychiatrists? Dr. Bostic: In general, we find that depressed kids are more likely to present as irritable rather than despondent. Now that doesn't mean you can say, "have you been irritable?", because a kid doesn't say, "yeah I've been irritable;" a kid acts irritable, and you'll typically hear a history of that irritability from other people.
TCR: How do you approach the psychiatric interview with children and adolescents? Dr. Bostic: As opposed to most adults, we find that kids tend not to be reliable reporters of externalizing symptoms of depression, while they tend to be better reporters of internalizing symptoms. What do I mean by internalizing symptoms? Anhedonia, poor self esteem. So a kid might say things like, "I don't enjoy hockey," or "I feel down on myself, I'm no good, I'm worthless." But when it comes to externalizing symptoms such as the neurovegetative symptoms of depression, like sleep or appetite changes, the younger the kid, the less reliable, which means that you have to rely on other people to identify those symptoms. And this means people who are really familiar with the kid's daily life, often more than just the parent or the guardian. A teacher, in my opinion, is often a very helpful reporter in these cases. In addition, younger kids will often somaticize symptoms, because they don't know how else to describe these internal states that don't make sense to them.
TCR: How do you diagnose depression in the pre-school age group? Dr. Bostic: We rarely diagnose pre-schoolers with depression. You might see a myriad of somatic complaints, or enormous functional impairment, and usually these kids are diagnosed as either ADHD or bipolar disorder. A key issue is always functional impairment-if a kid has been kicked out of multiple daycare situations, I'm often going to medicate, regardless of the age.
Depression in Children “We find that depressed kids are more likely to present as irritable rather than despondent.”
TCR: Those of us who have young children ourselves are all too familiar with age-appropriate irritability and tantruming. How do you differentiate a normal amount of acting out from pathology? Dr. Bostic: Kids whose meltdowns last less than 30 minutes-where they rant and rave for 5 minutes or so, and then they're "calmable downable," are one thing. The kids that end up with the diagnosis of bipolar disorder have tantrums that literally last for hours. Also, kids who have normal tantrums of childhood act up when their needs are frustrated, and that's not necessarily so with mood disordered kids, who sometimes exhibit what we informally call "unpremeditative aggression" and may become dangerously assaultive toward whoever or whatever is in front of them.
TCR: What about depressed latency age kids (ages 6-12)? Dr. Bostic: You'll see irritability and somatization. Usually there's more a sense of self-criticism and inadequacy than overt suicidal behavior.
TCR: What kinds of questions do you ask of this age group? Dr. Bostic: I ask "How do you in school? How do you do when you're playing sports?" Kids who are depressed will say, "I hate to do this, I hate to play sports, it's not any fun for me." Responses are pretty concrete at this age group. In adolescence you'll begin to hear things that show more reflection, like, "I'm depressed, I don't fit, I don't belong, I don't care if I live or die."
TCR: Let's move on to treatment issues. What's your reading of the tricyclic antidepressant (TCAs) literature for kids? Dr. Bostic: There have been about 13 controlled trials of TCAs with kids: six with children and seven with adolescents. Of interest to me is that when Tim Wilens and I looked at these studies (Bostic et al, Psych Clin NA, 6:175-191, 1999), there was about a 4% benefit of a given TCA over placebo in a latency age kid, but there was an 8% benefit in an adolescent. And once you get to adulthood the separation from placebo is about 20%, and becomes clinically significant. The fascinating thing is that these data are consistent with basic research going back to the 1970s in which researchers determined that the noradrenergic pathways are relatively undeveloped in young children, and mature gradually through adolescence and adulthood. This appears not true of serotonergic pathways, which mature at an early age. And, consistent with this, studies of SRI's (serotonin reuptake inhibitors) so far have not shown a differential response by age. So the SRIs are a better choice for young people than the TCAs.
TCR: Obviously there's recently been a lot of upheaval in the realm of SSRI use in kids, particularly with the recent pronouncement from the FDA suggesting that we not use Paxil for kids. Dr. Bostic: The Paxil issue emerged because GlaxoSmithKline, the manufacturer, elected to use adult rating scales in their pediatric depression studies, and these scales don't separate well from placebo in non-adult populations. So although the clinicians who took care of the 275 kids in the recent Keller study said "certain kids clearly seem to be better" based on the CGI (Clinician’s Global Impression scale), they didn't detect that difference on the 17-item Hamilton Depression Scale. And this is an enormous issue because when the British MHPA (Medicine Healthcare Products Regulatory Agency) and the FDA began looking at this data with Paxil they said, "wait a minute, there's no evidence that this drug has efficacy, and there could be an increased risk of suicidality here." Thirty three patients out of 1200 who had been in these Paxil studies described severe mood swings, suicidal thoughts and even suicidal behaviors, but none of the 33 people actually suicided. And of course, 8 of the 33 were actually on placebo, and never on Paxil.
TCR: What is the more appropriate rating scale to use? Dr. Bostic: The Childhood Depression Rating Scale (CDRS), which has been used in positive studies of Prozac, Zoloft, and Celexa, and the Montgomery Asberg Depression Rating Scale also appears a better measure for juveniles with depression than the Hamilton.
TCR: So do you believe that Paxil is actually effective for pediatric depression? Dr. Bostic: Yes, I do. But the FDA pronouncement has put researchers and clinicians in a difficult position. For example, it has had the effect of limiting studies, such as one study comparing Wellbutrin with Paxil in which the FDA recently intervened and said you cannot enroll anyone in the Paxil arm of that study. And clinically, if you see a patient, for example, who has had three family members respond to Paxil, it would make the most sense to start him on that, but given what the FDA has said, you really probably shouldn't. The other strange thing that came out of the FDA was the apparently contradictory advice that if someone was doing well on Paxil you aren't supposed to abruptly stop them, although I have heard reports of managed care companies refusing to allow someone under 18 to refill their Paxil, which of course is not an intelligent thing to do. If someone's doing well, you keep them on the drug.
TCR: Now that Zoloft has been shown effective, do you think they are going to go after the pediatric indication? Dr. Bostic: The people at Pfizer I've spoken with have said "no." This may be because the Zoloft patent will be running out soon and it may not be worth the regulatory expense for the company. However, it's interesting to note that Prozac was approved for kids for both OCD and depression in January third of 2003, after it had come off patent. Pfizer did however succeed in being able to add the depressed patients treated with Zoloft into the safety data of their package insert. The only other antidepressant currently moving toward an FDA indication for kids is Celexa/Lexapro through Forest. They've completed 1 Celexa study of about 174 juveniles with depression, and that study was positive, and they are almost finished with a larger Lexapro study (about 240 juveniles with depression). Both Pfizer (Zoloft) and Forest (Celexa/Lexapro) recently presented at the National Meeting of child psychiatry, and the data they presented did not suggest significant suicidal risks associated with Zoloft, Celexa, or Lexapro. But it's early, so it always makes sense to investigate suicidality in patients starting any antidepressant, and to attune family members to risk factors and to contact the clinician if they see withdrawal, preoccupations with death, or hear comments from the child that suggest suicidal thoughts or behaviors.