Modafinil reduces depression’s severity when taken with antidepressants
A new study has concluded that taking the drug modafinil, typically 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, was published online in the Journal of Clinical Psychiatry.
Approximately a third of depressed patients receive little or no benefit from taking antidepressants even when used in combination with psychological counseling. Furthermore, of those who respond to treatment, residual symptoms such as fatigue and trouble sleeping pose risk factors for relapse. The authors of the study believe that these individuals in particular would benefit the most from supplementing their antidepressants with modafinil.
Professor Barbara Sahakian from the University of Cambridge said, “Modafinil has actions on a number of neurotransmitter systems. This may explain why adding it to traditional anti-depressants, such as selective serotonin reuptake inhibitors, has beneficial effects on the symptoms experienced by depressed patients.”
“This is good news for individuals struggling to fight depression,” said Professor Cynthia Fu from University of East London, who undertook the research whilst at King’s College London. “Depression affects all aspects of life, leading to occupational and social disability at varying levels. It is particularly important that people receive effective treatment as the residual symptoms - e.g. fatigue, lack of concentration etc. - can persist and have a negative impact in people’s lives.”
For the research, the scientists reviewed various studies which had examined the use of modafinil as an add-on treatment for depression. The meta-analysis involved a total of 568 patients with unipolar depression and a total of 342 patients with bipolar depression. The analysis revealed that modafinil improved the severity of depression as well as remission rates. Modafinil also showed beneficial effects on fatigue and sleepiness, with the added benefit of the comparable side effects to placebo.
The research also revealed that the symptomatic benefits of modafinil might also have implications for improving the difficulty of functioning at work sometimes caused by depression. This is significant because depression is a major cause of absenteeism (absence due to sick leave) and presenteeism (present at work but not functioning as before).
‘Severity’ of depression
Defining the ‘degree’ or ‘severity’ of depression ie if it is mild, moderate or severe, requires an extensive medical judgement that involves the number, type, and severity of the symptoms present.
Mild depression usually causes symptoms that are detectable and impact upon our daily activities. We are less interested in doing things we previously enjoyed, unusual irritability, reduced motivation in work, home or social activities are common however we continue to function - just perhaps not as well as we normally would do when healthy.
Mild depression often goes undiagnosed because the symptoms are not considered to be ‘bad enough’ for people to think they may have depression and discuss it with their doctors or other people. However accurately diagnosing depression when it is mild, and treating it effectively at this stage can prevent the condition from worsening to become moderate or severe.
There are also more treatment options available for mild depression. Lifestyle changes such as regular exercise, relaxation, ensuring sufficient and regular sleep, etc are often sufficient. Natural therapies such as St John’s Wart may also be effective treatments for depression if it is diagnosed early - when ‘mild’.
Moderate depression can cause real difficulties with social, work and domestic activities. The characteristics described for mild depression are worse here - by definition. A reduced interest in normally pleasurable activities becomes no interest - a real lack of interest and motivation. Simple things start to require real effort or just get neglected.
With moderate depression there is usually a detectable reduction in self confidence and/or self esteem which can have a ‘snowball’ effect as we become less motivated and hence less productive. Often we start to worry about things unnecessarily such as performance at work, even if we are managing to maintain our previous standards, or more sensitive and susceptible to feeling hurt or offended within personal relationships.
Again, there are more treatment options available and the time it will take to recover from moderate depression will be less than if it is left untreated and develops into major depression. Cognitive Behavioural Therapy (CBT) can be very effective and some natural therapies may still be helpful, although it is essential that you discuss this with your doctor to ensure you use the most effective treatment option and don’t waste time, money and energy on treatments that aren’t doing anything. This only gives the illness an opportunity to worsen as it is not being effectively treated.
If medication is required, you are likely to be need a lower dose for moderate depression than for major depression. Lifestyle improvements always have a positive impact, however can take more effort to actually do as the depression becomes more severe.
Severe or Major depression causes considerable distress or agitation, loss of self-esteem or feelings of uselessness and guilt. We are unlikely to be able to continue with work, social and domestic activities. Severe (or Major) depression usually causes severe enough symptoms for a change to be noticeable by those around us even if we try to mask how we are feeling. A person with major depression will usually experience most, if not all of the symptoms listed on ‘Symptoms of depression’.
Suicide is a distinct and major danger. While we may be managing one moment, we can plummet very quickly into feelings of hopelessness and despair. It is common for people to feel that they are somehow responsible and ‘to blame’ for the way thery are feeling and believe that others are better off without them.
It is vital that professional help and treatment is sought as soon as possible and that treatment is adhered to. As with all major illnesses, during major depression we need additional support on a daily basis both in managing the symptoms and to provide help with treatment.
People with severe depressive episodes may also suffer from delusions, hallucinations or depressive stupor although these are less common.
Dr Muzaffer Kaser from the University of Cambridge added: “The next step is for longer trials to evaluate potential benefits of supplementing antidepressants with modafinil more comprehensively.”
Depression is a major global health problem. According to the World Health Organisation, it is estimated to be the second leading cause of disability worldwide by 2020. Recent studies revealed that depression represents more than a third of global burden of disease attributable to mental health problems*. The annual cost of mood disorders to the UK economy is estimated to be around £16 billion**. Disability caused by depression is mainly due to the negative impact on work and social functioning and its relapsing nature.
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Severe Depression does not indicate weak character and it should not be considered something shameful that needs to be hidden. Depression is not something that a person can control or prevent by willpower or determination. In it’s most severe forms, depression appears to be a chemical imbalance that may occur at any time, even when life is going well.
As depressive disorders become more severe, all the features in depressive episode occur with greater intensity. There is complete loss of function in social and occupational spheres. The patients in attention to basic hygiene and nutrition may give rise to fears for his well being. In addition, certain distinctive features may occur in the form of delusions and hallucinations; the disorder is then sometimes called psychotic depression.
The delusions of severe depressive disorders are concerned with the same themes as the non delusional thinking of moderate depressive disorders. Therefore they are termed mood congruent.
Symptoms of Severe Depression includes:
In severe depression sufferers will probably not function with any degree of reliability. The some of the common symptoms of severe depression are as follows:
considerable distress or agitation,
loss of self-esteem or feelings of uselessness and guilt,
They will tend to lack any desire to talk to others or to look after themselves,
They may show a great deal of restlessness and general agitation, but will not do anything constructive,
In some cases the feelings of unworthiness and self-disgust may lead sufferers to ‘hear voices’,
They may also believe that they have had visitations from the devil or other dark forces,
Suicidal thought.
People in this state are unable to lead any kind of normal life.
Notes to editors:
1. The paper ‘Modafinil Augmentation Therapy in Unipolar and Bipolar Depression: A Systematic Review and Meta-Analysis of Randomized Controlled Trials’ is published in the November edition of Journal of Clinical Psychiatry.
2. *Whiteford HA. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet doi:10.1016/S0140-6736(13)61611-6
**Fineberg, NA, et al. “The size, burden and cost of disorders of the brain in the UK.” Journal of Psychopharmacology 27.9 (2013): 761-770
3. Acknowledgements: Dr Kaser is a PhD student funded by IDB-Cambridge International Scholarship and he receives support from his affiliated institution, Bahcesehir University, Istanbul, Turkey. Dr Costafreda is supported by a National Institute for Health Research Clinical Lecturer post and receives research support funding from South London and Maudsley Biomedical Research Unit in Dementia. Professor Barbara J Sahakian is funded by a grant from the Wellcome Trust and the BCNI is jointly-funded by the Medical Research Council and Wellcome Trust. Professor Cynthia H.Y. Fu is funded by a personal Chair in the School of Psychology, UEL.
3. About King’s College 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 Sunday Times ‘Best University for Graduate Employment 2012/13’. A research-led university based in the heart of London, King’s has more than 25,000 students (of whom more than 10,000 are graduate students) from nearly 140 countries, and more than 6,500 employees. King’s is in the second phase of a £1 billion redevelopment programme which is transforming its estate.
King’s has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £554 million.
King’s has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile 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 Centre (AHSC) is a pioneering global collaboration between one of the world’s leading research-led universities and three of London’s most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services.
The College is in the midst of a five-year, £500 million fundraising campaign - World questions|King’s answers - created to address some of the most pressing challenges facing humanity as quickly as feasible. 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 is available at http://www.kcl.ac.uk/kingsanswers.
4. About the University of East London
The University of East London (UEL) is a global learning community with over 28,000 students from over 120 countries worldwide. Our vision is to achieve national and international recognition as a successful and inclusive university proud of its diversity, committed to new modes of learning which focus on students and enhance their employability, and renowned for our contribution to social, cultural and economic development, especially through our research and scholarship. We have a strong track-record in widening participation and working with industry.
By 2015 UEL aims to be the leading modern university for research in the UK. UEL is an innovative academic community, delivering high-quality research that is impactful, intellectually stimulating, socially relevant and for the public good. UEL is recognised by the academic community throughout the world for our high-quality research, theory and practice, and for our innovation and vitality.
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