Bupropion for Depression in Adolescents

Is bupropion a safe and effective antidepressant for adolescents 12 to 20 years of age?

Bupropion is an effective therapy for adolescents with major depressive disorder and may decrease rates of hospitalizations for depression and medication discontinuation. An increased risk of overdose and seizures may be possible for up to 24 hours after dosing.¹ Bupropion may be an option for adolescents with major depressive disorder, although those at increased risk of suicide, seizures, and eating disorders should be excluded. There may be additional benefits for weight loss, smoking cessation, and concurrent attention-deficit/hyperactivity disorder (ADHD). This is a key recommendation for clinicians for antidepressant therapy in adolescents 12 to 20 years of age. (Strength of Recommendation: B, patient-oriented evidence from meta-analysis and randomized trials.)

A 2019 retrospective chart review investigated the effectiveness and safety of bupropion for depressive disorders in children and adolescents.² The review included 127 participants with a mean age of 15.3 years. Two independent child psychiatrists confirmed a diagnosis of depressive disorder. Researchers used the Clinical Global Impressions-Depression-Severity Scale (CGI Depression Scale) to evaluate for changes with treatment. The CGI Depression Scale is a 7-point clinician-led assessment that evaluates the severity of and changes in mental illness (1 = normal, not at all ill, and 7 = extremely ill). The study found that 58 patients (45.7%) responded to treatment, defined by a score of less than 2. Among the patients determined to be responders, 82.8% had a primary diagnosis of major depression. Although 42.5% of participants reported adverse events, most spontaneously resolved within the 12-week study, and participants continued the medication. Importantly, 36.2% of participants discontinued bupropion because of irritability before completing 12 weeks of treatment.

In 2017, a retrospective observational study evaluated data in the National Poison Data System for overdoses that were “suspected suicide” in adolescents 13 to 19 years of age.³ Researchers identified suspected suicide attempts involving 2,253 patients taking bupropion and 1,496 taking tricyclic antidepressants. Patients on bupropion demonstrated a significantly increased risk of seizures compared with those on tricyclic antidepressants (30.7% vs. 3.9%; P < .01). Patients taking bupropion were less likely to develop hypotension (2.7% vs. 8.0%; P < .01) or require intubation (5.6% vs. 16.4%; P < .01) than those using tricyclic antidepressants, and the bupropion patients were more likely to be hospitalized (74.8% vs. 61.6%; P < .01) or have a serious medical outcome, such as hallucinations, hypertension, tachycardia, or seizures (19.3% vs. 10%; P < .01).

A 2022 Taiwanese retrospective cohort study investigated the effectiveness of antidepressants in adolescents younger than 20 years.⁴ Based on reimbursement medical claims from the National Health Insurance program, 16,981 individuals were identified with a diagnosis of major depressive disorder and were prescribed 1 of 10 antidepressants. Of this group, 736 were prescribed bupropion and had lower rates of hospitalization (adjusted hazard ratio [HR] = 0.32; 95% CI, 0.12 to 0.85) and discontinuation (adjusted HR = 0.91; 95% CI, 0.84 to 0.995) vs. those taking fluoxetine. These findings were similar in a subgroup analysis, with the younger subgroup (i.e., younger than 16 years) having no hospitalizations and decreased rates of hospitalization (adjusted HR = 0.35; 95% CI, 0.13 to 0.96) and discontinuation (adjusted HR = 0.90; 95% CI, 0.81 to 0.99) compared with fluoxetine in the older subgroup.

A 2019 analysis of the National Poison Data System compared suspected suicide attempts with selective serotonin reuptake inhibitors vs. bupropion in adolescents.¹ A total of 30,026 patients were part of the analysis, with bupropion use accounting for 11.7%. Compared with selective serotonin reuptake inhibitors, bupropion had a significantly increased association with suicide attempts leading to death (0.23% vs. 0%; P < .001) or other serious outcomes (58.1% vs. 19.0%; P < .001) and significantly increased individual associations with seizures (27.0% vs. 8.5%; P < .001), hallucinations (28.6% vs. 4.3%; P < .001), and the need for cardiopulmonary resuscitation (0.51% vs. 0.01%; P < .001) and intubation (4.9% vs. 0.3%; P < .001). However, a 2018 systematic review and network meta-analysis of 82 randomized controlled trials assessed the efficacy and tolerability of medications in adolescents (12 to 18 years of age) and children (5 to 11 years of age) for the treatment of ADHD (n = 11,018).⁵ This study focused on bupropion therapy for ADHD but helped answer the question of medication acceptability. Bupropion was found to be tolerable without a significant difference compared with placebo in children and adolescents (odds ratio = 1.51; 95% CI, 0.17 to 13.27).⁵