A new study published in the journal Mædica – a Journal of Clinical Medicine compared the antidepressant effects of modafinil versus citalopram for treating major depressive disorder (MDD).
The medications were equally effective at reducing depressive symptoms over a 6-week treatment period.
Key facts:
- 30 patients with MDD were treated with either modafinil or citalopram for 6 weeks
- Depression severity was measured with the Hamilton Depression Rating Scale (HDRS)
- Both medications significantly reduced HDRS scores over time
- There was no significant difference in efficacy between modafinil and citalopram
- Medications were equally effective regardless of patient age, gender, education level, etc.
What exactly is “Major Depressive Disorder”?
Major depressive disorder (MDD) is a common and serious mood disorder characterized by persistent feelings of sadness, hopelessness, and loss of interest in usual activities.
Symptoms must persist for at least 2 weeks and impair normal functioning to meet diagnostic criteria.
MDD affects over 16 million Americans each year. It is a leading cause of disability and carries risk of suicide.
Antidepressant medications and psychotherapy are first-line treatments for MDD.
Selective serotonin reuptake inhibitors (SSRIs) like citalopram are the most commonly prescribed antidepressants.
They can effectively treat depression, but side effects like sexual dysfunction often lead patients to discontinue treatment. This highlights the need for alternative medication options.
Citalopram vs. modafinil comparison (basics)
Citalopram is an SSRI antidepressant that works by increasing serotonin levels in the brain.
It is used to treat depression and approved for long-term use.
Common side effects include nausea, headache, insomnia, and sexual dysfunction.
Modafinil is a stimulant medication approved for treating sleep disorders like narcolepsy.
It acts on multiple neurotransmitters in the brain.
Modafinil is not FDA-approved for depression but several studies suggest it may reduce fatigue and improve mood in MDD when added to an antidepressant.
It has a mild side effect profile.
How the study compared citalopram & modafinil
This randomized clinical trial included 30 patients aged 18-65 diagnosed with MDD.
- 15 patients were treated with modafinil
- 15 patients were treated with citalopram
The starting dose was 100mg modafinil or 20mg citalopram daily.
After 1 week, the dose was increased to 200mg modafinil or 40mg citalopram.
The Hamilton Depression Rating Scale (HDRS) was used to assess depression severity before treatment and at 3 and 6 weeks.
HDRS scores range from 0 to 52, with higher scores indicating more severe depression.
Study Findings: Equal Antidepressant Effects
- Before treatment, the average HDRS score was 34.5, indicating severe depression.
- After 3 weeks of treatment, scores reduced to 28.1
- After 6 weeks of treatment, scores reduced to 22.1
The reductions in HDRS scores over time were statistically significant for both treatment groups.
However, there was no significant difference in efficacy between modafinil and citalopram at any timepoint.
In other words, both medications led to significant improvement in depression, but neither drug outperformed the other.
The antidepressant effects were similar regardless of patient characteristics like age, gender, education level, and marital status.
This study provides evidence that modafinil may be an effective alternative to traditional antidepressants like SSRIs for treating major depression.
Over 6 weeks, modafinil and citalopram:
- Produced significant reductions in depression severity
- Were equally effective at improving depressive symptoms
- Did not differ significantly in efficacy or side effects
- Worked similarly well regardless of patient demographics
These findings suggest the stimulant modafinil may have antidepressant properties comparable to the commonly used SSRI citalopram.
Larger and longer studies are still needed. But this research indicates modafinil is worth further exploration as a novel therapy for major depression.
How modafinil could benefit people with depression
Modafinil offers a few potential advantages over traditional antidepressants:
- Fewer sexual side effects than SSRIs
- Activation and energy-boosting effects
- Low abuse potential
For depression patients struggling with fatigue, sleepiness, and SSRI side effects, modafinil may represent an appealing alternative medication.
Of course, citalopram and other first-line antidepressant medications remain excellent options for treating MDD in many patients.
But having a wider variety of medications available gives doctors and patients more choices to find the optimal individualized treatment.
This study provides preliminary evidence that modafinil could expand the arsenal of pharmacotherapy options for major depression.
More research is still required to confirm its efficacy and safety for this off-label use.
Study Limitations and Future Research
While these results are promising, the study had several important limitations:
- Small sample size of only 30 patients
- Short 6-week treatment duration
- Lacked placebo control group for comparison
- Only examined one dose level of each medication
Larger and longer clinical trials are needed to fully evaluate modafinil as an antidepressant.
To build on these findings, future studies should:
- Enroll hundreds of participants with MDD
- Extend treatment to at least 12 weeks
- Include placebo control groups
- Compare multiple dose levels
- Assess long-term safety and discontinuation effects
Ideally, future research will also compare modafinil head-to-head against a wider variety of antidepressant medications.
Additionally, further evaluation of modafinil’s effects on cognition and neurobiology will help shed light on its mechanisms as an antidepressant.
Closing thoughts on modafinil’s potential for depression…
This small but well-designed trial provides initial evidence that modafinil could be an effective treatment for major depression.
Over a 6-week period, it performed comparably to the commonly prescribed antidepressant citalopram at reducing depressive symptoms.
Larger placebo-controlled studies are still required to confirm modafinil’s antidepressant efficacy.
But these findings indicate it may offer a promising alternative to SSRIs for patients who require activation or have side effect issues with traditional medications.
Modafinil is not currently FDA-approved for depression, but this research suggests it warrants further evaluation as a novel therapy for MDD.
References
- Study: Comparison between the efficacies of modafinil and citalopram in the treatment of major depression
- Authors: Hamzeh Rostami et al. (2022)
