From the Guidelines
The most effective approach for treating major depressive disorder (MDD) is a combination of pharmacologic and nonpharmacologic treatments, with cognitive-behavioral therapy (CBT) being a reasonable alternative to second-generation antidepressants (SGAs) as an initial treatment option. Studies have shown that CBT has no more—and probably fewer—adverse effects than SGAs, and lower relapse rates have been reported with CBT than SGAs 1.
When comparing SGAs with CBT, moderate-quality evidence from 5 trials showed no difference in response when comparing SGAs with CBT in patients with MDD after 8 to 52 weeks of treatment 1. Low-quality evidence from 3 trials showed no difference between remission rates and functional capacity for SGAs compared with CBT.
In terms of combination therapy, low-quality evidence from 2 trials showed no difference in response or remission when comparing monotherapy using SGAs with combination therapy using SGAs plus CBT in patients with MDD after 12 to 52 weeks of treatment 1. However, patients who received the combination therapy reported more improvement on work-functioning measures than those who received SGA monotherapy.
Some studies suggest that non-stimulant medications, such as atomoxetine, clonidine, and guanfacine, may be effective in treating ADHD, but their effect sizes are generally smaller than those of stimulants 1. These medications may be considered as second-line treatment options or as adjunctive therapy to stimulant medications.
For adults with alcohol or substance use disorders, a systematic review and meta-analysis found that combined pharmacotherapy and CBT was associated with improved clinical outcomes, and that CBT was superior to usual clinical management in the context of pharmacotherapy 1.
Key points to consider when making treatment decisions include:
- The potential benefits and risks of each treatment option
- The patient's symptom profile, preferences, and functional impairments
- The availability of evidence-based treatments, such as CBT
- The potential for combination therapy to improve treatment outcomes.
Overall, a comprehensive treatment plan that incorporates both pharmacologic and nonpharmacologic approaches, tailored to the individual patient's needs, is likely to be the most effective way to improve morbidity, mortality, and quality of life outcomes.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Comparative Efficacy of Add-on Medication and Non-Medication Methods
- The study 2 compared the efficacy of fluoxetine, cognitive-behavioral therapy (CBT), and their combination for adolescents with depression, and found that the combination of fluoxetine with CBT offered the most favorable tradeoff between benefit and risk.
- Another study 3 developed a data-driven algorithm for guiding selection between CBT, fluoxetine, and combination treatment for adolescent depression, and found that the algorithm successfully identified subgroups of patients that respond preferentially to specific types of treatment.
- A study 4 on combination pharmacotherapy for adult ADHD found that adjunct treatment of d-methylphenidate to stimulant medications extended the duration of therapeutic effect, and adjunct treatment of mirtazapine to stimulant medications reduced associated insomnia.
- The study 5 evaluated the efficacy of fluoxetine monotherapy in attention-deficit/hyperactivity disorder and comorbid non-bipolar mood disorders in children and adolescents, and found that fluoxetine was associated with significant decreases in the severity of depressive symptoms and ADHD symptoms.
- A narrative review 6 on methylphenidate for attention-deficit/hyperactivity disorder in adults found that methylphenidate was moderately effective both against the core ADHD symptoms and the accompanying emotion regulation deficits.
Key Findings
- Combination treatment (e.g. fluoxetine with CBT) may be more effective than monotherapy (e.g. fluoxetine alone or CBT alone) for certain conditions, such as adolescent depression 2.
- Data-driven algorithms can be used to guide selection between different treatment options (e.g. CBT, fluoxetine, and combination treatment) for adolescent depression 3.
- Add-on medication (e.g. d-methylphenidate or mirtazapine) can be effective in extending the duration of therapeutic effect or reducing associated symptoms in adult ADHD 4.
- Fluoxetine monotherapy can be effective in reducing depressive symptoms and ADHD symptoms in children and adolescents with comorbid non-bipolar mood disorders 5.
- Methylphenidate is a commonly used and effective medication for ADHD in adults, with a multimodal mechanism of action and moderate efficacy against core ADHD symptoms and emotion regulation deficits 6.