Modafinil reduces the severity of depression when taken with antidepressants (2023)

A new study has found that taking the drug modafinil, commonly used to treat sleep disorders, in combination with antidepressants reduces the severity of depression more effectively than taking antidepressants alone. The study, a collaboration between the universities of Cambridge and East London and King's College London, has been published online atJournal of Clinical Psychiatry.

About a third of depressed patients have little or no benefit from antidepressants, even when used in conjunction with psychological counseling. In addition, among those who respond to treatment, residual symptoms such as fatigue and difficulty sleeping are risk factors for relapse. The study authors believe that these individuals in particular would benefit most from supplementing their antidepressants with modafinil.

Professor Barbara Sahakian from the University of Cambridge said: "Modafinil acts on several neurotransmitter systems. This may explain why adding it to traditional antidepressants, such as selective serotonin reuptake inhibitors, has a beneficial effect on the symptoms experienced by patients with depression…

"This is good news for people struggling with depression," said Professor Cynthia Fu of the University of East London, who led the research at King's College London. “Depression affects all aspects of life, leading to occupational and social disability at various levels. It is especially important that people receive effective treatment, as residual symptoms - e.g. fatigue, lack of concentration, etc. - can persist and have a negative impact on life."

As part of their research, the researchers looked at several studies that looked at the use of modafinil as a treatment to support depression. A total of 568 patients with unipolar depression and a total of 342 patients with bipolar depression participated in the meta-analysis. The analysis showed that modafinil improves depression severity as well as remission rates. Modafinil has also shown beneficial effects on fatigue and sleepiness, with the added benefit of side effects comparable to placebo.

Studies have also shown that the symptomatic benefits of modafinil can also have the effect of improving the difficulties in functioning at work that are sometimes caused by depression. This is important because depression is a major cause of absenteeism (absence due to illness) and presenteeism (being present at work but not working as well as before).

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dr. Muzaffer Kaser of the University of Cambridge added: "The next step is larger trials to more comprehensively assess the potential benefits of supplementing with the antidepressant modafinil."

Depression is a major global health problem. According to the World Health Organization, it is estimated that by 2020 it will be the second leading cause of disability in the world. Recent studies have shown that depression accounts for more than a third of the global burden of mental health-related illness*. The annual cost of mood disorders to the UK economy is estimated at around £16 billion**. Disability caused by depression is mainly due to the negative impact on work and social functioning and its recurrent nature.


For more information, please contact:

Genevieve Maul, University of Cambridge Communications Office
Tel: direct, +44 (0) 1223 765542, +44 (0) 1223 332300
Mobile: +44 (0) 7774 017464

Notes to editors:

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1. The article "Modafinil Augmentation Therapy in Unipolar and Bipolar Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials" was published in the November issue of the journalJournal of Clinical Psychiatry.

2. * Whiteford HA. The Global Burden of Disease Associated with Mental Disorders and Substance Use: Findings from the 2010 Global Burden of Disease Study.Lancetadoi:10.1016/S0140-6736(13)61611-6

**Fineberg, NA et al. "The extent, burden and cost of brain disorders in the UK".Journal of Psychopharmacology27,9 (2013): 761-770

3. Acknowledgments: Dr. Kaser is a PhD student funded by the IDB-Cambridge International Scholarship and receives support from his affiliated institution, Bahcesehir University in Istanbul, Turkey. dr. Costafreda is a clinical lecturer at the National Institute for Health Research and receives research support from South London and the Maudsley Dementia Biomedical Research Unit. Professor Barbara J Sahakian is funded by a grant from the Wellcome Trust and BCNI is jointly funded by the Medical Research Council and the Wellcome Trust. Professor Cynthia HY Fu is funded by a personal chair at UEL's Department of Psychology.

3.EyeKing's College in London

King's College London is one of the top 20 universities in the world (2013/14 QS World University Rankings) and the fourth oldest in England. It is the "Best Postgraduate University in the Labor Market 2012/13" according to the Sunday Times. A research-driven university based in the heart of London, King's has over 25,000 students (of which over 10,000 are postgraduates) from nearly 140 countries and over 6,500 employees. King's is in the second phase of a £1 billion regeneration scheme turning its fortunes around.

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King's has an excellent reputation for providing world-class teaching and cutting-edge research. The 2008 UK Universities Assessment Survey ranked 23 faculties in the top quartile of UK universities. over half of our academic staff work in faculties that are ranked in the top 10 per cent in the UK in their field and therefore can be described as world-leading. The college is one of the top seven UK universities in terms of research revenue and has a total annual income of nearly £554 million.

King's has a particular reputation in the humanities, law, sciences (including a wide range of health fields such as psychiatry, medicine, nursing and dentistry) and social sciences, including international relations. He played an important role in many developments that have shaped modern life, such as the discovery of the structure of DNA and the research that led to the development of radio, television, cell phones and radar.

King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Center (AHSC) is a pioneering global collaboration between one of the world's leading research universities and three of London's most successful NHS Foundation trusts, including leading teaching hospitals and comprehensive mental health services. For more information visit:

The college is in the midst of a five-year £500m fundraising campaign - World Affairs | King's Answers - Created to solve some of humanity's most pressing challenges as quickly as possible. The campaign's five priority areas are neuroscience and mental health, leadership and society, cancer, global power and children's health. More information about the campaign can be found at

4.ForEast London University

The University of East London (UEL) is a global learning community with over 28,000 students from over 120 countries around the world. Our vision is to achieve national and international recognition as a successful and inclusive university, proud of its diversity, committed to new ways of learning that are student centered and employable, and known for our contributions to social, cultural and economic, in particular through our research and scholarship. We have a good track record of increasing participation and collaboration with industry.

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By 2015, UEL aims to become the UK's leading contemporary research university. UEL is an innovative academic community that provides high-quality research that impacts, intellectually stimulates, is socially relevant, and serves the common good. UEL is recognized by the academic community around the world for our high-quality research, theory and practice, as well as our innovation and vitality.


Journal of Clinical Psychiatry

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Can you take modafinil with antidepressants? ›

The combination caused few adverse events, with nausea and headache being the most common. Conclusion: Modafinil combined with an SSRI at treatment initiation may enhance the onset and degree of symptom benefit in patients with MDD and fatigue.

Is modafinil effective for depression? ›

The adverse events were no different from placebo. Modafinil is an effective augmentation strategy for acute depressive episodes, including for symptoms of fatigue, in both unipolar and bipolar disorders.

Does modafinil reduce serotonin? ›

They found that modafinil is able to enhance serotonin release, but it does not cause serotonin release or reuptake on its own and suggested that modafinil increased electrosecretory coupling in neurons.

Can I take Zoloft and modafinil? ›

No interactions were found between modafinil and Zoloft.

Does modafinil damage dopamine? ›

At clinically relevant doses, modafinil significantly increases dopamine in the human brain by blocking dopamine transporters.

Does modafinil improve mood? ›

Modafinil reduces excessive somnolence and enhances mood in patients with myotonic dystrophy. Neurology 59: 1876–1880.

What can you not mix with modafinil? ›

Taking opioids like oxycodone, fentanyl and hydrocodone alongside Modafinil can result in complications. Patients mixing Modafinil with these drugs may experience a drop in Modafinil plasma concentrations and lead to decreased effectiveness.

Can I take Lexapro and modafinil? ›

Interactions between your drugs

Modafinil may increase the blood levels and effects of escitalopram.

What stimulants can you take with antidepressants? ›

D-amphetamine (Dexedrine) and methylphenidate (Ritalin) are stimulants used to treat depression. They can be used alone, but they may also be used in combination with antidepressant medications.

What medication should not be taken with antidepressants? ›

Some of the medicines that can interact with some SSRIs include:
  • non-steroidal anti-inflammatory drugs (NSAIDs) – a common type of painkiller that includes ibuprofen, diclofenac or naproxen.
  • antiplatelets – a type of medicine used to prevent blood clots, such as low-dose aspirin and clopidogrel.


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5. Going Back On Antidepressants Has Changed My Life (ssri sertraline/zoloft medication)
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