Open trial of bupropion SR in adolescent major depression

Journal of Child and Adolescent Psychiatric Nursing, Jul-Sep 2003 by Glod, Carol A, Lynch, Arlene, Flynn, Elizabeth, Berkowitz, Cynthia, Baldessarini, Ross J

Methods of clinical assessment and definitions of response may contribute to the inconsistency in antidepressant trials in pediatric depression reviewed above. In most trials, symptoms have been assessed using clinician-rated categorical outcome measures such as the CGI scale (Thase & Rush, 1995), or with standard symptom rating scales developed for adult depression (such as the HDRS) or, less commonly, for child depression (Children's Depression Rating Scale-Revised (CDRS-R) (Poznanski, Freeman, & Mokros, 1985). In addition to a clinician and patient-based categorical outcome measure (CGI) in the present study, we used a continuous measure of illness severity (SIGH-SAD scale) (Williams et al, 1992), and a primary measure of outcome involving major improvement virtually to symptomatic remission (to a total score of

This assessment instrument, commonly employed in research on seasonal depression, is based on the standard HDRS expanded to include features (particularly anergy, hypersomnia and hyperphagia) common encountered in pediatric depressive illness (Swedo et al., 1997), and traditionally associated with adult seasonal affective disorder (Williams et al., 1992), "atypical" depression, as well as early-onset bipolar depression (Faedda et al, 1995). In previous research, this rating scale proved more sensitive to depressive symptoms commonly encountered in pediatric and adolescent depressives than the standard HDRS (Swedo et al). Moreover, the added features pertaining to anergy and hyperphagia are particularly likely to show beneficial effects of the activating effects of the antidepressant bupropion (Baldessarini, 2001). These common features of juvenile depression may or may not respond to alternative agents, including the TCAs, which have been notoriously unsuccessful in studies of early onset depression in children and adolescents, as reviewed above.

In addition to yielding a high response rate, bupropion SR was also well tolerated by depressed adolescents and did not induce mania in any subject. It has less propensity than other types of antidepressants to induce sexual dysfunction than SRIs, and less risk of adverse cardiovascular effects than the TCAs (Baldessarini, 2001), making it an attractive alternative for use in depressed juveniles, including those with co-morbid ADHD, as was found in some of the present subjects (see Table 1). The apparent acceptability of this antidepressant may be especially important in treating adolescents suffering a first episode of depression, whose acceptance and adherence to medication are notoriously improbable (Lewinsohn et al., 2000).

Given an unsatisfactory basis for confident differentiation of juvenile affective and behavioral disorders (Faedda et al, 1995; Papolos & Papolos, 2000), bupropion SR may be useful if it limits the risk of mania, rapid-cycling, or other affective instability in juvenile bipolar disorder patients presenting in depression. Such relative safety of bupropion has been suggested for adult bipolar patients (Sachs et al, 1994; Stoll et al., 1994), but it remains to be tested directly in pediatric subjects. Safety in bipolar patients may be especially important for treating young depressed patients who may be at particularly high risk for unrecognized bipolar disorder or bipolar precursor syndromes, sometimes presenting in misdiagnosed mixed, dysphoric, agitated bipolar states (Faedda et al.; Papolos & Papolos). Geller, Fox, and Clark (1994) found that 32% of 79 depressed prepubertal children developed recognizable bipolar I or II disorder by an average age of 11 years. Bipolarity is suggested by such risk factors as family history of affective or psychotic illness and by irritability and worsening emotional or behavioral instability when treated with an antidepressant or stimulant without a mood stabilizer (Faedda et al.; McConville et al., 1996).